Metabolism in cancer metastasis: bioenergetics, biosynthesis, and beyond

Wiley Interdisciplinary Reviews: Systems Biology and Medicine

Volumn 10, Issue 2, 2018, Pages

  Teoh, Shao Thing ^a   Lunt, Sophia Y ^a  

^a Michigan State University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; GLUTAMINE; GLYCINE; METHIONINE; PROLINE; SARCOSINE; SERINE; REACTIVE OXYGEN METABOLITE;

AMINO ACID METABOLISM; CARCINOGENESIS; CITRIC ACID CYCLE; FATTY ACID METABOLISM; GLYCOLYSIS; HUMAN; METABOLISM; METASTASIS; MITOCHONDRION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; PENTOSE PHOSPHATE CYCLE; REVIEW; TUMOR IMMUNITY; ANIMAL; IMMUNOLOGY; NEOPLASM; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CITRIC ACID CYCLE; HUMANS; NEOPLASM METASTASIS; NEOPLASMS; PENTOSE PHOSPHATE PATHWAY; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 85042147734     PISSN: 19395094     EISSN: 1939005X     Source Type: Journal    
DOI: 10.1002/wsbm.1406     Document Type: Review

References (308)

1. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell 2017, 168:670–691.
2. Seyfried TN, Huysentruyt LC. On the origin of cancer metastasis. Crit Rev Oncog 2013, 18:43–73.
3. Mehlen P, Puisieux A. Metastasis: a question of life or death. Nat Rev Cancer 2006, 6:449–458.
4. Brabletz T, Lyden D, Steeg PS, Werb Z. Roadblocks to translational advances on metastasis research. Nat Med 2013, 19:1104–1109.
5. Giancotti FG. Mechanisms governing metastatic dormancy and reactivation. Cell 2013, 155:750–764.
6. Fidler IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 2003, 3:453–458.
7. Paget S. The distribution of secondary growths in cancer of the breast. Lancet 1889, 133:571–573.
8. Biddle A, Mackenzie IC. Cancer stem cells and EMT in carcinoma. Cancer Metastasis Rev 2012, 31:285–293.
9. Abell AN, Johnson GL. Implications of mesenchymal cells in cancer stem cell populations: relevance to EMT. Curr Pathobiol Rep 2014, 2:21–26.
10. Davis FM, Stewart TA, Thompson EW, Monteith GR. Targeting EMT in cancer: opportunities for pharmacological intervention. Trends Pharmacol Sci 2014, 35:479–488.
11. Nieto MA, Huang Ruby Y-J, Jackson Rebecca A, Thiery JP. EMT: 2016. Cell 2016, 166:21–45.
12. Fischer KR, Durrans A, Lee S, Sheng J, Li F, Wong STC, Choi H, El Rayes T, Ryu S, Troeger J, et al. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature 2015, 527:472–476.
13. Zheng X, Carstens JL, Kim J, Scheible M, Kaye J, Sugimoto H, Wu C-C, LeBleu VS, Kalluri R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature 2015, 527:525–530.
14. Tsuji T, Ibaragi S, Shima K, Hu MG, Katsurano M, Sasaki A, Hu G-f. Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth. Cancer Res 2008, 68:10377–10386.
15. Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, Petrocca F, Martinvalet D, Song E, Lim B, Lieberman J. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One 2009, 4:e7181.
16. Greaves M, Maley CC. Clonal evolution in cancer. Nature 2012, 481:306–313.
17. Beerenwinkel N, Schwarz RF, Gerstung M, Markowetz F. Cancer evolution: mathematical models and computational inference. Syst Biol 2015, 64:e1–e25.
18. Cunningham JJ, Brown JS, Vincent TL, Gatenby RA. Divergent and convergent evolution in metastases suggest treatment strategies based on specific metastatic sites. Evol Med Public Health 2015, 2015:76–87.
19. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P, Olivier M. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum Mutat 2007, 28:622–629.
20. Williams AB, Schumacher B. p53 in the DNA damage repair process. Cold Spring Harb Perspect Med 2016, 6. https://doi.org/10.1101/cshperspect.a026070.
21. Nowell PC. The clonal evolution of tumor cell populations. Science 1976, 194:23–28.
22. Zhao Z-M, Zhao B, Bai Y, Iamarino A, Gaffney SG, Schlessinger J, Lifton RP, Rimm DL, Townsend JP. Early and multiple origins of metastatic lineages within primary tumors. Proc Natl Acad Sci USA 2016, 113:2140–2145.
23. Nassar D, Latil M, Boeckx B, Lambrechts D, Blanpain C. Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma. Nat Med 2015, 21:946–954.
24. Ramaswamy S, Ross KN, Lander ES, Golub TR. A molecular signature of metastasis in primary solid tumors. Nat Genet 2003, 33:49–54.
25. Hunter KW, Alsarraj J. Gene expression profiles and breast cancer metastasis: a genetic perspective. Clin Exp Metastasis 2009, 26:497–503.
26. Bernards R, Weinberg RA. Metastasis genes: a progression puzzle. Nature 2002, 418:823.
27. Hurst DR, Welch DR. Metastasis suppressor genes: at the interface between the environment and tumor cell growth. Int Rev Cell Mol Biol 2011, 286:107–180.
28. Scott Kenneth L, Nogueira C, Heffernan Timothy P, van Doorn R, Dhakal S, Hanna Jason A, Min C, Jaskelioff M, Xiao Y, Wu C-J, et al. Proinvasion metastasis drivers in early-stage melanoma are oncogenes. Cancer Cell 2011, 20:92–103.
29. Steeg PS, Theodorescu D. Metastasis: a therapeutic target for cancer. Nat Clin Pract Oncol 2008, 5:206–219.
30. Gupta GP, Minn AJ, Kang Y, Siegel PM, Serganova I, Cordón-Cardo C, Olshen AB, Gerald WL, Massagué J. Identifying site-specific metastasis genes and functions. Cold Spring Harb Symp Quant Biol 2005, 70:149–158.
31. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massagué J. Genes that mediate breast cancer metastasis to lung. Nature 2005, 436:518–524.
32. Metallo CM, Heiden MGV. Metabolism strikes back: metabolic flux regulates cell signaling. Genes Dev 2010, 24:2717–2722.
33. Ward PS, Thompson CB. Signaling in control of cell growth and metabolism. Cold Spring Harb Perspect Biol 2012, 4. https://doi.org/10.1101/cshperspect.a026070.
34. Lu C, Thompson CB. Metabolic regulation of epigenetics. Cell Metab 2012, 16:9–17.
35. Keating ST, El-Osta A. Epigenetics and metabolism. Circ Res 2015, 116:715–736.
36. Fiaschi T, Chiarugi P. Oxidative stress, tumor microenvironment, and metabolic reprogramming: a diabolic liaison. Int J Cell Biol 2012, 2012:e762825.
37. Fukumura D, Jain RK. Tumor microenvironment abnormalities: causes, consequences, and strategies to normalize. J Cell Biochem 2007, 101:937–949.
38. Bailey KM, Wojtkowiak JW, Hashim AI, Gillies RJ. Targeting the metabolic microenvironment of tumors. Adv Pharmacol 2012, 65:63–107.
39. Davidson SM, Papagiannakopoulos T, Olenchock BA, Heyman JE, Keibler MA, Luengo A, Bauer MR, Jha AK, O'Brien JP, Pierce KA, et al. Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer. Cell Metab 2016, 23:517–528.
40. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv 2016, 2:e1600200.
41. Elia I, Schmieder R, Christen S, Fendt S-M. Organ-specific cancer metabolism and its potential for therapy. Handb Exp Pharmacol 2016, 233:321–353.
42. Lorendeau D, Christen S, Rinaldi G, Fendt S-M. Metabolic control of signalling pathways and metabolic auto-regulation. Biol Cell 2015, 107:251–272.
43. Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 2009, 9:274–284.
44. Christen S, Lorendeau D, Schmieder R, Broekaert D, Metzger K, Veys K, Elia I, Buescher JM, Orth MF, Davidson SM, et al. Breast cancer-derived lung metastases show increased pyruvate carboxylase-dependent anaplerosis. Cell Rep 2016, 17:837–848.
45. Kim HM, Jung WH, Koo JS. Site-specific metabolic phenotypes in metastatic breast cancer. J Transl Med 2014, 12:354.
46. Elia I, Fendt S-M. In vivo cancer metabolism is defined by the nutrient microenvironment. Transl Cancer Res 2016, 5(Suppl 6):S1284–S1287.
47. Liu W, Vivian CJ, Brinker AE, Hampton KR, Lianidou E, Welch DR. Microenvironmental influences on metastasis suppressor expression and function during a metastatic cell's journey. Cancer Microenviron 2014, 7:117–131.
48. Molon B, Calì B, Viola A. T cells and cancer: how metabolism shapes immunity. Front Immunol 2016, 7. https://doi.org/10.3389/fimmu.2017.01183.
49. Altenberg B, Greulich KO. Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes. Genomics 2004, 84:1014–1020.
50. Ogawa H, Nagano H, Konno M, Eguchi H, Koseki JUN, Kawamoto K, Nishida N, Colvin H, Tomokuni A, Tomimaru Y, et al. The combination of the expression of hexokinase 2 and pyruvate kinase M2 is a prognostic marker in patients with pancreatic cancer. Mol Clin Oncol 2015, 3:563–571.
51. Chaika NV, Yu F, Purohit V, Mehla K, Lazenby AJ, DiMaio D, Anderson JM, Yeh JJ, Johnson KR, Hollingsworth MA, et al. Differential expression of metabolic genes in tumor and stromal components of primary and metastatic loci in pancreatic adenocarcinoma. PLoS One 2012, 7:e32996.
52. Sato-Tadano A, Suzuki T, Amari M, Takagi K, Miki Y, Tamaki K, Watanabe M, Ishida T, Sasano H, Ohuchi N. Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1α and Ki-67. Cancer Sci 2013, 104:1380–1388.
53. Nevo I, Oberthuer A, Botzer E, Sagi-Assif O, Maman S, Pasmanik-Chor M, Kariv N, Fischer M, Yron I, Witz IP. Gene-expression-based analysis of local and metastatic neuroblastoma variants reveals a set of genes associated with tumor progression in neuroblastoma patients. Int J Cancer 2010, 126:1570–1581.
54. Anderson M, Marayati R, Moffitt R, Yeh JJ. Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic cancer. Oncotarget 2017, 8:56081–56094.
55. Botzer LE, Maman S, Sagi-Assif O, Meshel T, Nevo I, Yron I, Witz IP. Hexokinase 2 is a determinant of neuroblastoma metastasis. Br J Cancer 2016, 114:759–766.
56. Zhou C-F, Li X-B, Sun H, Zhang B, Han Y-S, Jiang Y, Zhuang Q-L, Fang J, Wu G-H. Pyruvate kinase type M2 is upregulated in colorectal cancer and promotes proliferation and migration of colon cancer cells. IUBMB Life 2012, 64:775–782.
57. Yu G, Yu W, Jin G, Xu D, Chen Y, Xia T, Yu A, Fang W, Zhang X, Li Z, et al. PKM2 regulates neural invasion of and predicts poor prognosis for human hilar cholangiocarcinoma. Mol Cancer 2015, 14:193.
58. Lu W, Cao Y, Zhang Y, Li S, Gao J, Wang X-A, Mu J, Hu Y-P, Jiang L, Dong P, et al. Up-regulation of PKM2 promote malignancy and related to adverse prognostic risk factor in human gallbladder cancer. Sci Rep 2016, 6:26351.
59. Liu WR, Tian MX, Yang LX, Lin YL, Jin L, Ding ZB, Shen YH, Peng YF, Gao DM, Zhou J, et al. PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma. Oncotarget 2015, 6:846–861.
60. Zhang B, Chen JY, Chen DD, Wang GB, Shen P. Tumor type M2 pyruvate kinase expression in gastric cancer, colorectal cancer and controls. World J Gastroenterol 2004, 10:1643–1646.
61. Sun H, Zhu A, Zhang L, Zhang J, Zhong Z, Wang F. Knockdown of PKM2 suppresses tumor growth and invasion in lung adenocarcinoma. Int J Mol Sci 2015, 16:24574–24587.
62. Shin YK, Yoo BC, Hong YS, Chang HJ, Jung KH, Jeong SY, Park JG. Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5-fluorouracil resistance. Electrophoresis 2009, 30:2182–2192.
63. Duan H-F, Hu X-W, Chen J-L, Gao L-H, Xi Y-Y, Lu Y, Li J-F, Zhao S-R, Xu J-J, Chen H-P, et al. Antitumor activities of TEM8-Fc: an engineered antibody-like molecule targeting tumor endothelial marker 8. J Natl Cancer Instit 2007, 99:1551–1555.
64. Heiden MGV, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010, 329:1492–1499.
65. Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, et al. Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat Genet 2011, 43:869–874.
66. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang J-K, Shen M, Bellinger G, Sasaki AT, Locasale JW, Auld DS, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011, 334:1278–1283.
67. Wu X, Somlo G, Yu Y, Palomares MR, Li AX, Zhou W, Chow A, Yen Y, Rossi JJ, Gao H, et al. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer. J Transl Med 2012, 10:42.
68. Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, Chow A, O'Connor STF, Li S, Chin AR, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol 2015, 17:183–194.
69. Watanabe H, Takehana K, Date M, Shinozaki T, Raz A. Tumor cell autocrine motility factor is the neuroleukin/phosphohexose isomerase polypeptide. Cancer Res 1996, 56:2960–2963.
70. Sun Y-J, Chou C-C, Chen W-S, Wu R-T, Meng M, Hsiao C-D. The crystal structure of a multifunctional protein: phosphoglucose isomerase/autocrine motility factor/neuroleukin. Proc Natl Acad Sci USA 1999, 96:5412–5417.
71. Schulz LC, Bahr JM. Glucose-6-phosphate isomerase is necessary for embryo implantation in the domestic ferret. Proc Natl Acad Sci USA 2003, 100:8561–8566.
72. Repiso A, Andrés R, Climent F, Ureña JM. Expression patterns in mouse embryos of neuroleukin/glucose-6-phosphate isomerase and autocrine motility factor receptor. Anat Histol Embryol 2008, 37:380–382.
73. Xu W, Seiter K, Feldman E, Ahmed T, Chiao JW. The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase. Blood 1996, 87:4502–4506.
74. Gurney M, Heinrich S, Lee M, Yin H. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science 1986, 234:566–574.
75. Liotta LA, Mandler R, Murano G, Katz DA, Gordon RK, Chiang PK, Schiffmann E. Tumor cell autocrine motility factor. Proc Natl Acad Sci USA 1986, 83:3302–3306.
76. Tsutsumi S, Hogan V, Nabi IR, Raz A. Overexpression of the autocrine motility factor/phosphoglucose isomerase induces transformation and survival of NIH-3T3 fibroblasts. Cancer Res 2003, 63:242–249.
77. Tsutsumi S, Fukasawa T, Yamauchi H, Kato T, Kigure W, Morita H, Asao T, Kuwano H. Phosphoglucose isomerase enhances colorectal cancer metastasis. Int J Oncol 2009, 35:1117–1121.
78. Tsutsumi S, Gupta SK, Hogan V, Tanaka N, Nakamura KT, Nabi IR, Raz A. The enzymatic activity of phosphoglucose isomerase is not required for its cytokine function. FEBS Lett 2003, 534:49–53.
79. Baumann M, Kappl A, Lang T, Brand K, Siegfried W, Paterok E. The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. Cancer Invest 1990, 8:351–356.
80. Guirguis R, Schiffmann E, Liu B, Birkbeck D, Engel J, Liotta L. Detection of autocrine motility factor in urine as a marker of bladder cancer. J Natl Cancer Inst 1988, 80:1203–1211.
81. Nabi IR, Watanabe H, Raz A. Identification of B16-F1 melanoma autocrine motility-like factor receptor. Cancer Res 1990, 50:409–414.
82. Hirono Y, Fushida S, Yonemura Y, Yamamoto H, Watanabe H, Raz A. Expression of autocrine motility factor receptor correlates with disease progression in human gastric cancer. Br J Cancer 1996, 74:2003–2007.
83. Maruyama K, Watanabe H, Shiozaki H, Takayama T, Gofuku J, Yano H, Inoue M, Tamura S, Raz A, Monden M. Expression of autocrine motility factor receptor in human esophageal squamous cell carcinoma. Int J Cancer 1995, 64:316–321.
84. Tsutsumi S, Gupta SK, Hogan V, Collard JG, Raz A. Activation of small GTPase Rho is required for autocrine motility factor signaling. Cancer Res 2002, 62:4484–4490.
85. Torimura T, Ueno T, Kin M, Harada R, Nakamura T, Kawaguchi T, Harada M, Kumashiro R, Watanabe H, Avraham R, et al. Autocrine motility factor enhances hepatoma cell invasion across the basement membrane through activation of β1 integrins. Hepatology 2001, 34:62–71.
86. Ahmad A, Aboukameel A, Kong D, Wang Z, Sethi S, Chen W, Sarkar FH, Raz A. Phosphoglucose isomerase/autocrine motility factor mediates epithelial-mesenchymal transition regulated by miR-200 in breast cancer cells. Cancer Res 2011, 71:3400–3409.
87. Chesney J. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase and tumor cell glycolysis. Curr Opin Clin Nutr Metab Care 2006, 9:535–539.
88. Tudzarova S, Colombo SL, Stoeber K, Carcamo S, Williams GH, Moncada S. Two ubiquitin ligases, APC/C-Cdh1 and SKP1-CUL1-F (SCF)-β-TrCP, sequentially regulate glycolysis during the cell cycle. Proc Natl Acad Sci USA 2011, 108:5278–5283.
89. Calvo MN, Bartrons R, Castaño E, Perales JC, Navarro-Sabaté A, Manzano A. PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells. FEBS Lett 2006, 580:3308–3314.
90. Cantelmo AR, Conradi L-C, Brajic A, Goveia J, Kalucka J, Pircher A, Chaturvedi P, Hol J, Thienpont B, Teuwen L-A, et al. Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy. Cancer Cell 2016, 30:968–985.
91. Payen VL, Porporato PE, Baselet B, Sonveaux P. Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway. Cell Mol Life Sci 2016, 73:1333–1348.
92. Walenta S, Schroeder T, Mueller-Klieser W. Lactate in solid malignant tumors: potential basis of a metabolic classification in clinical oncology. Curr Med Chem 2004, 11:2195–2204.
93. Walenta S, Salameh A, Lyng H, Evensen JF, Mitze M, Rofstad EK, Mueller-Klieser W. Correlation of high lactate levels in head and neck tumors with incidence of metastasis. Am J Pathol 1997, 150:409–415.
94. Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001, 51:349–353.
95. Schwickert G, Walenta S, Sundfør K, Rofstad EK, Mueller-Klieser W. Correlation of high lactate levels in human cervical cancer with incidence of metastasis. Cancer Res 1995, 55:4757–4759.
96. Walenta S, Wetterling M, Lehrke M, Schwickert G, Sundfør K, Rofstad EK, Mueller-Klieser W. High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers. Cancer Res 2000, 60:916–921.
97. Walenta S, Chau T-V, Schroeder T, Lehr H-A, Kunz-Schughart LA, Fuerst A, Mueller-Klieser W. Metabolic classification of human rectal adenocarcinomas: a novel guideline for clinical oncologists? J Cancer Res Clin Oncol 2003, 129:321–326.
98. Goetze K, Walenta S, Ksiazkiewicz M, Kunz-Schughart LA, Mueller-Klieser W. Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int J Oncol 2011, 39:453–463.
99. Baumann F, Leukel P, Doerfelt A, Beier CP, Dettmer K, Oefner PJ, Kastenberger M, Kreutz M, Nickl-Jockschat T, Bogdahn U, et al. Lactate promotes glioma migration by TGF-β2-dependent regulation of matrix metalloproteinase-2. Neuro Oncol 2009, 11:368–380.
100. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, Frank PG, Flomenberg N, Howell A, Martinez-Outschoorn UE, et al. Ketones and lactate “fuel” tumor growth and metastasis. Cell Cycle 2010, 9:3506–3514.
101. Gatenby RA, Gillies RJ. Why do cancers have high aerobic glycolysis? Nat Rev Cancer 2004, 4:891–899.
102. Ibrahim Hashim A, Cornnell HH, Coelho Ribeiro ML, Abrahams D, Cunningham J, Lloyd M, Martinez GV, Gatenby RA, Gillies RJ. Reduction of metastasis using a non-volatile buffer. Clin Exp Metastasis 2011, 28:841–849.
103. Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, Hashim AI, Morse DL, Raghunand N, Gatenby RA, et al. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res 2009, 69:2260–2268.
104. Nokin M-J, Durieux F, Peixoto P, Chiavarina B, Peulen O, Blomme A, Turtoi A, Costanza B, Smargiasso N, Baiwir D, et al. Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis. Elife 2016, 5:e19375.
105. Chiavarina B, Nokin M-J, Bellier J, Durieux F, Bletard N, Sherer F, Lovinfosse P, Peulen O, Verset L, Dehon R, et al. Methylglyoxal-mediated stress correlates with high metabolic activity and promotes tumor growth in colorectal cancer. Int J Mol Sci 2017, 18:213.
106. Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY, Gao S, Puigserver P, Brugge JS. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 2009, 461:109–113.
107. Chen EI, Hewel J, Krueger JS, Tiraby C, Weber MR, Kralli A, Becker K, Yates JR, Felding-Habermann B. Adaptation of energy metabolism in breast cancer brain metastases. Cancer Res 2007, 67:1472–1486.
108. Cha YJ, Jung WH, Koo JS. Differential site-based expression of pentose phosphate pathway-related proteins among breast cancer metastases. Dis Markers 2017, 2017:10.
109. White NMA, Newsted DW, Masui O, Romaschin AD, Siu KWM, Yousef GM. Identification and validation of dysregulated metabolic pathways in metastatic renal cell carcinoma. Tumor Biol 2014, 35:1833–1846.
110. Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ, Morrison SJ. Oxidative stress inhibits distant metastasis by human melanoma cells. Nature 2015, 527:186–191.
111. Gal KL, Ibrahim MX, Wiel C, Sayin VI, Akula MK, Karlsson C, Dalin MG, Akyürek LM, Lindahl P, Nilsson J, et al. Antioxidants can increase melanoma metastasis in mice. Sci Transl Med 2015, 7:308re308.
112. Frenkel K. Carcinogen-mediated oxidant formation and oxidative DNA damage. Pharmacol Ther 1992, 53:127–166.
113. Wiseman H, Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 1996, 313:17–29.
114. Langbein S, Frederiks WM, zur Hausen A, Popa J, Lehmann J, Weiss C, Alken P, Coy JF. Metastasis is promoted by a bioenergetic switch: new targets for progressive renal cell cancer. Int J Cancer 2008, 122:2422–2428.
115. Langbein S, Zerilli M, zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, Popa J, Ternullo MP, Steidler A, Weiss C, et al. Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 2006, 94:578–585.
116. Xu X, zur Hausen A, Coy JF, Löchelt M. Transketolase-like protein 1 (TKTL1) is required for rapid cell growth and full viability of human tumor cells. Int J Cancer 2009, 124:1330–1337.
117. Krockenberger M, Honig A, Rieger L, Coy JF, Sutterlin M, Kapp M, Horn E, Dietl J, Kammerer U. Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases. Int J Gynecol Cancer 2007, 17:101–106.
118. Zerilli M, Amato MC, Martorana A, Cabibi D, Coy JF, Cappello F, Pompei G, Russo A, Giordano C, Rodolico V. Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases. Cancer 2008, 113:936–944.
119. McDonald OG, Li X, Saunders T, Tryggvadottir R, Mentch SJ, Warmoes MO, Word AE, Carrer A, Salz TH, Natsume S, et al. Epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis. Nat Genet 2017, 49:367–376.
120. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011, 11:325–337.
121. Singh RK, Srivastava A, Kalaiarasan P, Manvati S, Chopra R, Bamezai RNK. mtDNA germ line variation mediated ROS generates retrograde signaling and induces pro-cancerous metabolic features. Sci Rep 2014, 4:6571.
122. Zamzami N, Marchetti P, Castedo M, Decaudin D, Macho A, Hirsch T, Susin SA, Petit PX, Mignotte B, Kroemer G. Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death. J Exp Med 1995, 182:367–377.
123. Feeley KP, Bray AW, Westbrook DG, Johnson LW, Kesterson RA, Ballinger SW, Welch DR. Mitochondrial genetics regulate breast cancer tumorigenicity and metastatic potential. Cancer Res 2015, 75:4429–4436.
124. Weber GF. Molecular mechanisms of metastasis. Cancer Lett 2008, 270:181–190.
125. Caneba CA, Bellance N, Yang L, Pabst L, Nagrath D. Pyruvate uptake is increased in highly invasive ovarian cancer cells under anoikis conditions for anaplerosis, mitochondrial function, and migration. Am J Physiol Endocrinol Metab 2012, 303:E1036–E1052.
126. Porporato PE, Payen VL, Perez-Escuredo J, De Saedeleer CJ, Danhier P, Copetti T, Dhup S, Tardy M, Vazeille T, Bouzin C, et al. A mitochondrial switch promotes tumor metastasis. Cell Rep 2014, 8:754–766.
127. Richardson AD, Yang C, Osterman A, Smith JW. Central carbon metabolism in the progression of mammary carcinoma. Breast Cancer Res Treat 2008, 110:297–307.
128. Simões RV, Serganova IS, Kruchevsky N, Leftin A, Shestov AA, Thaler HT, Sukenick G, Locasale JW, Blasberg RG, Koutcher JA, et al. Metabolic plasticity of metastatic breast cancer cells: adaptation to changes in the microenvironment. Neoplasia 2015, 17:671–684.
129. Lunt SY, Heiden MGV. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 2011, 27:441–464.
130. Weber GF. Metabolism in cancer metastasis. Int J Cancer 2016, 138:2061–2066.
131. Glinsky GV, Glinsky VV. Apoptosis and metastasis: a superior resistance of metastatic cancer cells to programmed cell death. Cancer Lett 1996, 101:43–51.
132. Takaoka A, Adachi M, Okuda H, Sato S, Yawata A, Hinoda Y, Takayama S, Reed JC, Imai K. Anti-cell death activity promotes pulmonary metastasis of melanoma cells. Oncogene 1997, 14:2971–2977.
133. Wong CW, Lee A, Shientag L, Yu J, Dong Y, Kao G, Al-Mehdi AB, Bernhard EJ, Muschel RJ. Apoptosis: an early event in metastatic inefficiency. Cancer Res 2001, 61:333–338.
134. He B, Mirza M, Weber GF. An osteopontin splice variant induces anchorage independence in human breast cancer cells. Oncogene 2005, 25:2192–2202.
135. Loenarz C, Schofield CJ. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol 2008, 4:152–156.
136. Carey BW, Finley LWS, Cross JR, Allis CD, Thompson CB. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 2015, 518:413–416.
137. Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 2010, 29:4741–4751.
138. Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704–715.
139. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GRS, Chandel NS. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 2010, 107:8788–8793.
140. Wang J-B, Erickson JW, Fuji R, Ramachandran S, Gao P, Dinavahi R, Wilson KF, Ambrosio ALB, Dias SMG, Dang CV, et al. Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell 2010, 18:207–219.
141. Dang L, White DW, Gross S, Bennett BD, Bittinger MA, Driggers EM, Fantin VR, Jang HG, Jin S, Keenan MC, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009, 462:739.
142. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009, 360:765–773.
143. Ward PS, Cross JR, Lu C, Weigert O, Abel-Wahab O, Levine RL, Weinstock DM, Sharp KA, Thompson CB. Identification of additional IDH mutations associated with oncometabolite R(−)-2-hydroxyglutarate production. Oncogene 2012, 31:2491–2498.
144. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009, 361:1058–1066.
145. Hirata M, Sasaki M, Cairns RA, Inoue S, Puviindran V, Li WY, Snow BE, Jones LD, Wei Q, Sato S, et al. Mutant IDH is sufficient to initiate enchondromatosis in mice. Proc Natl Acad Sci USA 2015, 112:2829–2834.
146. Grassian AR, Lin F, Barrett R, Liu Y, Jiang W, Korpal M, Astley H, Gitterman D, Henley T, Howes R, et al. Isocitrate dehydrogenase (IDH) mutations promote a reversible ZEB1/microRNA (miR)-200-dependent epithelial-mesenchymal transition (EMT). J Biol Chem 2012, 287:42180–42194.
147. Colvin H, Nishida N, Konno M, Haraguchi N, Takahashi H, Nishimura J, Hata T, Kawamoto K, Asai A, Tsunekuni K, et al. Oncometabolite D-2-hydroxyglurate directly induces epithelial-mesenchymal transition and is associated with distant metastasis in colorectal cancer. Sci Rep 2016, 6:36289.
148. Yang H, Ye D, Guan K-L, Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: mechanistic insights and clinical perspectives. Clin Cancer Res 2012, 18:5562–5571.
149. Janeway KA, Kim SY, Lodish M, Nosé V, Rustin P, Gaal J, Dahia PLM, Liegl B, Ball ER, Raygada M, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci USA 2011, 108:314–318.
150. Castro-Vega LJ, Buffet A, de Cubas D, Cascón AA, Menara M, Khalifa E, Amar L, Azriel S, Bourdeau I, et al. Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet 2014, 23:2440–2446.
151. Letouzé E, Martinelli C, Loriot C, Burnichon N, Abermil N, Ottolenghi C, Janin M, Menara M, Nguyen An T, Benit P, et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 2013, 23:739–752.
152. Sciacovelli M, Gonçalves E, Johnson TI, Zecchini VR, da Costa ASH, Gaude E, Drubbel AV, Theobald SJ, Abbo SR, Tran MGB, et al. Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature 2016, 537:544–547.
153. Aspuria P-JP, Lunt SY, Väremo L, Vergnes L, Gozo M, Beach JA, Salumbides B, Reue K, Wiedemeyer WR, Nielsen J, et al. Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism. Cancer Metab 2014, 2:21.
154. King A, Selak MA, Gottlieb E. Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 2006, 25:4675–4682.
155. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim S-H, Ito S, Yang C, Wang P, Xiao M-T, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell 2011, 19:17–30.
156. Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, Pan Y, Simon MC, Thompson CB, Gottlieb E. Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-α prolyl hydroxylase. Cancer Cell 2005, 7:77–85.
157. Semenza GL. HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010, 20:51–56.
158. Fu Y, Zheng Y, Li K, Huang R, Zheng S, An N, Liang A. Mutations in isocitrate dehydrogenase 2 accelerate glioma cell migration via matrix metalloproteinase-2 and 9. Biotechnol Lett 2012, 34:441–446.
159. Kaelin WG. Cancer and altered metabolism: potential importance of HIF and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb Symp Quant Biol 2011, 76:335–345.
160. LeBleu VS, O'Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis Marcia C, de Carvalho FM, Damascena A, Domingos Chinen LT, Rocha RM, et al. PGC-1α mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol 2014, 16:992–1003.
161. Rodrigues MF, Obre E, Melo FHM, Santos GC, Galina A, Jasiulionis MG, Rossignol R, Rumjanek FD, Amoêdo ND. Enhanced OXPHOS, glutaminolysis and β-oxidation constitute the metastatic phenotype of melanoma cells. Biochem J 2016, 473:703–715.
162. Barbi de Moura M, Vincent G, Fayewicz SL, Bateman NW, Hood BL, Sun M, Suhan J, Duensing S, Yin Y, Sander C, et al. Mitochondrial respiration – an important therapeutic target in melanoma. Plos One 2012, 7:e40690.
163. Santidrian AF, Matsuno-Yagi A, Ritland M, Seo BB, LeBoeuf SE, Gay LJ, Yagi T, Felding-Habermann B. Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J Clin Invest 2013, 123:1068–1081.
164. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J-I. ROS-generating mitochondrial DNA mutations can regulate tumor cell metastasis. Science 2008, 320:661–664.
165. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012, 48:158–167.
166. Wellen KE, Thompson CB. Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell 2010, 40:323–332.
167. Brunelle JK, Bell EL, Quesada NM, Vercauteren K, Tiranti V, Zeviani M, Scarpulla RC, Chandel NS. Oxygen sensing requires mitochondrial ROS but not oxidative phosphorylation. Cell Metab 2005, 1:409–414.
168. Porporato PE, Sonveaux P. Paving the way for therapeutic prevention of tumor metastasis with agents targeting mitochondrial superoxide. Mol Cell Oncol 2015, 2:e968043.
169. Giannoni E, Buricchi F, Grimaldi G, Parri M, Cialdai F, Taddei ML, Raugei G, Ramponi G, Chiarugi P. Redox regulation of anoikis: reactive oxygen species as essential mediators of cell survival. Cell Death Differ 2008, 15:867–878.
170. Ogura M, Yamaki J, Homma Miwako K, Homma Y. Mitochondrial c-Src regulates cell survival through phosphorylation of respiratory chain components. Biochem J 2012, 447:281–289.
171. Meloche S, Pouysségur J. The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene 2007, 26:3227–3239.
172. Comito G, Calvani M, Giannoni E, Bianchini F, Calorini L, Torre E, Migliore C, Giordano S, Chiarugi P. HIF-1α stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells. Free Radic Biol Med 2011, 51:893–904.
173. Berra E, Richard DE, Gothié E, Pouysségur J. HIF-1-dependent transcriptional activity is required for oxygen-mediated HIF-1α degradation. FEBS Lett 2001, 491:85–90.
174. Kamarajugadda S, Stemboroski L, Cai Q, Simpson NE, Nayak S, Tan M, Lu J. Glucose oxidation modulates anoikis and tumor metastasis. Mol Cell Biol 2012, 32:1893–1907.
175. Gaude E, Frezza C. Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival. Nat Commun 2016, 7:13041.
176. Dupuy F, Tabariès S, Andrzejewski S, Dong Z, Blagih J, Annis Matthew G, Omeroglu A, Gao D, Leung S, Amir E, et al. PDK1-dependent metabolic reprogramming dictates metastatic potential in breast cancer. Cell Metab 2015, 22:577–589.
177. Fu Y-M, Meadows GG. Specific amino acid dependency regulates the cellular behavior of melanoma. J Nutr 2007, 137:1591S–1596S.
178. Medina MÁ, Márquez J, Núñez^de Castro I. Interchange of amino acids between tumor and host. Biochem Med Metab Biol 1992, 48:1–7.
179. Board M, Humm S, Newsholme EA. Maximum activities of key enzymes of glycolysis, glutaminolysis, pentose phosphate pathway and tricarboxylic acid cycle in normal, neoplastic and suppressed cells. Biochem J 1990, 265:503–509.
180. Liu W, Le A, Hancock C, Lane AN, Dang CV, Fan TW-M, Phang JM. Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci USA 2012, 109:8983–8988.
181. Liu G, Zhu J, Yu M, Cai C, Zhou Y, Yu M, Fu Z, Gong Y, Yang B, Li Y, et al. Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients. J Transl Med 2015, 13:144.
182. Yang L, Moss T, Mangala LS, Marini J, Zhao H, Wahlig S, Armaiz-Pena G, Jiang D, Achreja A, Win J, et al. Metabolic shifts toward glutamine regulate tumor growth, invasion and bioenergetics in ovarian cancer. Mol Syst Bio 2014, 10:728.
183. Cacace A, Sboarina M, Vazeille T, Sonveaux P. Glutamine activates STAT3 to control cancer cell proliferation independently of glutamine metabolism. Oncogene 2017, 36:2074–2084.
184. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, et al. Glutamine supports pancreatic cancer growth through a Kras-regulated metabolic pathway. Nature 2013, 496:101–105.
185. Ulanet DB, Couto K, Jha A, Choe S, Wang A, Woo H-K, Steadman M, DeLaBarre B, Gross S, Driggers E, et al. Mesenchymal phenotype predisposes lung cancer cells to impaired proliferation and redox stress in response to glutaminase inhibition. PLoS One 2014, 9:e115144.
186. Townsend DM, Tew KD. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 2003, 22:7369–7375.
187. Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, Pronzato MA, Marinari UM, Domenicotti C. Role of Glutathione in Cancer Progression and Chemoresistance. Oxid Med Cell Longev 2013, 2013:e972913.
188. Wheeler GL, Quinn KA, Perrone G, Dawes IW, Grant CM. Glutathione regulates the expression of γ-glutamylcysteine synthetase via the Met4 transcription factor. Mol Microbio 2002, 46:545–556.
189. Liu W, Hancock CN, Fischer JW, Harman M, Phang JM. Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine nucleotides. Sci Rep 2015, 5:17206.
190. Elia I, Broekaert D, Christen S, Boon R, Radaelli E, Orth MF, Verfaillie C, Grünewald TGP, Fendt S-M. Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells. Nat Commun 2017, 8:15267.
191. Liu Y, Borchert GL, Surazynski A, Hu C-A, Phang JM. Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling. Oncogene 2006, 25:5640–5647.
192. Liu W, Glunde K, Bhujwalla ZM, Raman V, Sharma A, Phang JM. Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments. Cancer Res 2012, 72:3677–3686.
193. Dewaele M, Maes H, Agostinis P. ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy. Autophagy 2010, 6:838–854.
194. Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, Ristow M. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab 2012, 15:451–465.
195. Comes S, Gagliardi M, Laprano N, Fico A, Cimmino A, Palamidessi A, De Cesare D, De Falco S, Angelini C, Scita G, et al. L-Proline induces a mesenchymal-like invasive program in embryonic stem cells by remodeling H3K9 and H3K36 methylation. Stem Cell Rep 2013, 1:307–321.
196. Ghosh Z, Huang M, Hu S, Wilson KD, Dey D, Wu JC. Dissecting the oncogenic potential of human embryonic and induced pluripotent stem cell derivatives. Cancer Res 2011, 71:5030–5039.
197. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 2008, 40:499–507.
198. Mecham JO, Rowitch D, Wallace CD, Stern PH, Hoffman RM. The metabolic defect of methionine dependence occurs frequently in human tumor cell lines. Biochem Biophys Res Commun 1983, 117:429–434.
199. Hoffman RM. Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. Biochim Biophys Acta 1984, 738:49–87.
200. Shiraki N, Shiraki Y, Tsuyama T, Obata F, Miura M, Nagae G, Aburatani H, Kume K, Endo F, Kume S. Methionine metabolism regulates maintenance and differentiation of human pluripotent stem cells. Cell Metab 2014, 19:780–794.
201. Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB, Mootha VK. Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science 2012, 336:1040–1044.
202. Fan J, Ye J, Kamphorst JJ, Shlomi T, Thompson CB, Rabinowitz JD. Quantitative flux analysis reveals folate-dependent NADPH production. Nature 2014, 510:298–302.
203. Maddocks Oliver DK, Labuschagne Christiaan F, Adams Peter D, Vousden KH. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Mol Cell 2016, 61:210–221.
204. Pollari S, Käkönen S-M, Edgren H, Wolf M, Kohonen P, Sara H, Guise T, Nees M, Kallioniemi O. Enhanced serine production by bone metastatic breast cancer cells stimulates osteoclastogenesis. Breast Cancer Res Treat 2011, 125:421–430.
205. Kozlow W, Guise TA. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia 2005, 10:169–180.
206. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 2009, 457:910–914.
207. McDunn JE, Li Z, Adam K-P, Neri BP, Wolfert RL, Milburn MV, Lotan Y, Wheeler TM. Metabolomic signatures of aggressive prostate cancer. Prostate 2013, 73:1547–1560.
208. Koutros S, Meyer TE, Fox SD, Issaq HJ, Veenstra TD, Huang W-Y, Yu K, Albanes D, Chu LW, Andriole G, et al. Prospective evaluation of serum sarcosine and risk of prostate cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Carcinogenesis 2013, 34:2281–2285.
209. Lucarelli G, Fanelli M, Larocca AMV, Germinario CA, Rutigliano M, Vavallo A, Selvaggi FP, Bettocchi C, Battaglia M, Ditonno P. Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml. Prostate 2012, 72:1611–1621.
210. Stabler S, Koyama T, Zhao Z, Martinez-Ferrer M, Allen RH, Luka Z, Loukachevitch LV, Clark PE, Wagner C, Bhowmick NA. Serum methionine metabolites are risk factors for metastatic prostate cancer progression. PLoS One 2011, 6:e22486.
211. Cao D-L, Ye D-W, Zhang H-L, Zhu Y, Wang Y-X, Yao X-D. A multiplex model of combining gene-based, protein-based, and metabolite-based with positive and negative markers in urine for the early diagnosis of prostate cancer. Prostate 2011, 71:700–710.
212. Bianchi F, Dugheri S, Musci M, Bonacchi A, Salvadori E, Arcangeli G, Cupelli V, Lanciotti M, Masieri L, Serni S, et al. Fully automated solid-phase microextraction–fast gas chromatography–mass spectrometry method using a new ionic liquid column for high-throughput analysis of sarcosine and N-ethylglycine in human urine and urinary sediments. Anal Chim Acta 2011, 707:197–203.
213. Wu H, Liu T, Ma C, Xue R, Deng C, Zeng H, Shen X. GC/MS-based metabolomic approach to validate the role of urinary sarcosine and target biomarkers for human prostate cancer by microwave-assisted derivatization. Anal Bioanal Chem 2011, 401:635–646.
214. Ankerst DP, Liss M, Zapata D, Hoefler J, Thompson IM, Leach RJ. A case control study of sarcosine as an early prostate cancer detection biomarker. BMC Urol 2015, 15:99.
215. Jentzmik F, Stephan C, Lein M, Miller K, Kamlage B, Bethan B, Kristiansen G, Jung K. Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression. J Urol 2011, 185:706–711.
216. Issaq HJ, Veenstra TD. Is sarcosine a biomarker for prostate cancer? J Sep Sci 2011, 34:3619–3621.
217. Hewavitharana AK. Re: Florian Jentzmik, Carsten Stephan, Kurt Miller, et al. Sarcosine in urine after digital rectal examination fails as a marker in prostate cancer detection and identification of aggressive tumours. Eur Urol 2010;58:12–8. Eur Urol 2010, 58:e39–e40.
218. Khan AP, Rajendiran TM, Ateeq B, Asangani IA, Athanikar JN, Yocum AK, Mehra R, Siddiqui J, Palapattu G, Wei JT, et al. The role of sarcosine metabolism in prostate cancer progression. Neoplasia 2013, 15:491–501.
219. Song YH, Shiota M, Kuroiwa K, Naito S, Oda Y. The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer. Mod Pathol 2011, 24:1272–1280.
220. Green T, Chen X, Ryan S, Asch AS, Ruiz-Echevarría MJ. TMEFF2 and SARDH cooperate to modulate one carbon metabolism and invasion of prostate cancer cells. Prostate 2013, 73:10.
221. Corbin JM, Ruiz-Echevarría MJ. One-carbon metabolism in prostate cancer: the role of androgen signaling. Int J Mol Sci 2016, 17:1208.
222. Putluri N, Shojaie A, Vasu VT, Nalluri S, Vareed SK, Putluri V, Vivekanandan-Giri A, Byun J, Pennathur S, Sana TR, et al. Metabolomic profiling reveals a role for androgen in activating amino acid metabolism and methylation in prostate cancer cells. PLoS One 2011, 6:e21417.
223. Heger Z, Merlos Rodrigo MA, Michalek P, Polanska H, Masarik M, Vit V, Plevova M, Pacik D, Eckschlager T, Stiborova M, et al. Sarcosine up-regulates expression of genes involved in cell cycle progression of metastatic models of prostate cancer. PLoS One 2016, 11:e0165830.
224. Yoon JK, Kim DH, Koo JS. Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer. J Transl Med 2014, 12:149.
225. Cha YJ, Kim DH, Jung WH, Koo JS. Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer. Int J Clin Exp Pathol 2014, 7:7824–7833.
226. Flavin R, Peluso S, Nguyen PL, Loda M. Fatty acid synthase as a potential therapeutic target in cancer. Fut Oncol 2010, 6:551–562.
227. Sounni Nor E, Cimino J, Blacher S, Primac I, Truong A, Mazzucchelli G, Paye A, Calligaris D, Debois D, De Tullio P, et al. Blocking lipid synthesis overcomes tumor regrowth and metastasis after antiangiogenic therapy withdrawal. Cell Metab 2014, 20:280–294.
228. Nath A, Chan C. Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers. Sci Rep 2016, 6:18669.
229. Liu W, Beck BH, Vaidya KS, Nash KT, Feeley KP, Ballinger SW, Pounds KM, Denning WL, Diers AR, Landar A, et al. Metastasis suppressor KISS1 appears to reverse the Warburg effect by enhancing mitochondrial biogenesis. Cancer Res 2014, 74:954–963.
230. Pascual G, Avgustinova A, Mejetta S, Martín M, Castellanos A, Attolini CS-O, Berenguer A, Prats N, Toll A, Hueto JA, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 2017, 541:41–45.
231. Antalis CJ, Uchida A, Buhman KK, Siddiqui RA. Migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification. Clin Exp Metastasis 2011, 28:733–741.
232. Park JH, Vithayathil S, Kumar S, Sung P-L, Dobrolecki LE, Putluri V, Bhat VB, Bhowmik SK, Gupta V, Arora K, et al. Fatty acid oxidation-driven Src links mitochondrial energy reprogramming and regulation of oncogenic properties in triple negative breast cancer. Cell Rep 2016, 14:2154–2165.
233. Jiang L, Xiao L, Sugiura H, Huang X, Ali A, Kuro-o M, Deberardinis RJ, Boothman DA. Metabolic reprogramming during TGFβ1-induced epithelial-to-mesenchymal transition. Oncogene 2015, 34:3908–3916.
234. Hedegaard M, Krafft C, Ditzel HJ, Johansen LE, Hassing S, Popp J. Discriminating isogenic cancer cells and identifying altered unsaturated fatty acid content as associated with metastasis status, using k-means clustering and partial least squares-discriminant analysis of Raman maps. Anal Chem 2010, 82:2797–2802.
235. You S, Tu H, Zhao Y, Liu Y, Chaney EJ, Marjanovic M, Boppart SA. Raman spectroscopic analysis reveals abnormal fatty acid composition in tumor micro- and macroenvironments in human breast and rat mammary cancer. Sci Rep 2016, 6:32922.
236. Rose DP, Connolly JM, Meschter CL. Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. J Natl Cancer Inst 1991, 83:1491–1495.
237. Rose DP, Connolly JM, Rayburn J, Coleman M. Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice. J Natl Cancer Inst 1995, 87:587–592.
238. Rose DP, Connolly JM, Coleman M. Effect of omega-3 fatty acids on the progression of metastases after the surgical excision of human breast cancer cell solid tumors growing in nude mice. Clin Cancer Res 1996, 2:1751–1756.
239. Mandal CC, Ghosh-Choudhury T, Yoneda T, Choudhury GG, Ghosh-Choudhury N. Fish oil prevents breast cancer cell metastasis to bone. Biochem Biophys Res Commun 2010, 402:602–607.
240. Hwang J-K, Yu H-N, Noh E-M, Kim J-M, Hong O-Y, Youn HJ, Jung SH, Kwon K-B, Kim J-S, Lee Y-R. DHA blocks TPA-induced cell invasion by inhibiting MMP-9 expression via suppression of the PPAR-γ/NF-κB pathway in MCF-7 cells. Oncol Lett 2017, 13:243–249.
241. Kang KS, Wang P, Yamabe N, Fukui M, Jay T, Zhu BT. Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation. PLoS One 2010, 5:e10296.
242. Hannafon BN, Carpenter KJ, Berry WL, Janknecht R, Dooley WC, Ding W-Q. Exosome-mediated microRNA signaling from breast cancer cells is altered by the anti-angiogenesis agent docosahexaenoic acid (DHA). Mol Cancer 2015, 14:133.
243. Lvd W, Arends MJ, Campbell AD, Bald T, Wardle-Jones H, Griggs N, Velasco-Herrera MDC, Tüting T, Sansom OJ, Karp NA, et al. Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. Nature 2017, 541:233–236.
244. Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, Greenberg PD. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA 2002, 99:16168–16173.
245. Crespo J, Sun H, Welling TH, Tian Z, Zou W. T cell anergy, exhaustion, senescence and stemness in the tumor microenvironment. Curr Opin Immunol 2013, 25:214–221.
246. Herbel C, Patsoukis N, Bardhan K, Seth P, Weaver JD, Boussiotis VA. Clinical significance of T cell metabolic reprogramming in cancer. Clin Transl Med 2016, 5:29.
247. Macintyre AN, Rathmell JC. Activated lymphocytes as a metabolic model for carcinogenesis. Cancer Metab 2013, 1:5.
248. Cham CM, Driessens G, O'Keefe JP, Gajewski TF. Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells. Eur J Immunol 2008, 38:2438–2450.
249. Chang C-H, Qiu J, O'Sullivan D, Buck MD, Noguchi T, Curtis JD, Chen Q, Gindin M, Gubin MM, van der Windt GJW, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015, 162:1229–1241.
250. Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, et al. Inhibitory effect of tumor cell–derived lactic acid on human T cells. Blood 2007, 109:3812–3819.
251. Ho P-C, Bihuniak JD, Macintyre AN, Staron M, Liu X, Amezquita R, Tsui Y-C, Cui G, Micevic G, Perales JC, et al. Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses. Cell 2015, 162:1217–1228.
252. Mbongue JC, Nicholas DA, Torrez TW, Kim N-S, Firek AF, Langridge WHR. The role of indoleamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines 2015, 3:703–729.
253. Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003, 9:1269–1274.
254. Munn DH, Shafizadeh E, Attwood JT, Bondarev I, Pashine A, Mellor AL. Inhibition of T cell proliferation by macrophage tryptophan catabolism. J Exp Med 1999, 189:1363–1372.
255. Fallarino F, Grohmann U, Vacca C, Orabona C, Spreca A, Fioretti MC, Puccetti P. T cell apoptosis by kynurenines. Adv Exp Med Biol 2003, 527:183–190.
256. Terness P, Bauer TM, Röse L, Dufter C, Watzlik A, Simon H, Opelz G. Inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells. J Exp Med 2002, 196:447–457.
257. Fallarino F, Volpi C, Zelante T, Vacca C, Calvitti M, Fioretti MC, Puccetti P, Romani L, Grohmann U. IDO Mediates TLR9-driven protection from experimental autoimmune diabetes. J Immunol 2009, 183:6303–6312.
258. Yan Y, Zhang G-X, Gran B, Fallarino F, Yu S, Li H, Cullimore ML, Rostami A, Xu H. IDO upregulates regulatory T cells via tryptophan catabolite and suppresses encephalitogenic T cell responses in experimental autoimmune encephalomyelitis. J Immunol 2010, 185:5953–5961.
259. Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA. An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 2010, 185:3190–3198.
260. Soliman H, Mediavilla-Varela M, Antonia S. Indoleamine 2,3-dioxygenase: is it an immune suppressor? Cancer J 2010, 16:354–359.
261. Speeckaert R, Vermaelen K, van Geel N, Autier P, Lambert J, Haspeslagh M, van Gele M, Thielemans K, Neyns B, Roche N, et al. Indoleamine 2,3-dioxygenase, a new prognostic marker in sentinel lymph nodes of melanoma patients. Eur J Cancer 2012, 48:2004–2011.
262. Mansfield AS, Heikkila PS, Vaara AT, von Smitten KA, Vakkila JM, Leidenius MH. Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer. BMC Cancer 2009, 9:231.
263. Jia Y, Wang H, Wang Y, Wang T, Wang M, Ma M, Duan Y, Meng X, Liu L. Low expression of Bin1, along with high expression of IDO in tumor tissue and draining lymph nodes, are predictors of poor prognosis for esophageal squamous cell cancer patients. Int J Cancer 2015, 137:1095–1106.
264. Tanizaki Y, Kobayashi A, Toujima S, Shiro M, Mizoguchi M, Mabuchi Y, Yagi S, Minami S, Takikawa O, Ino K. Indoleamine 2,3-dioxygenase promotes peritoneal metastasis of ovarian cancer by inducing an immunosuppressive environment. Cancer Sci 2014, 105:966–973.
265. Ryu HS, Park YS, Park HJ, Chung YR, Yom CK, Ahn S-H, Park YJ, Park SH, Park SY. Expression of indoleamine 2,3-dioxygenase and infiltration of FOXP3+ regulatory T cells are associated with aggressive features of papillary thyroid microcarcinoma. Thyroid 2014, 24:1232–1240.
266. Chen J-Y, Li C-F, Kuo C-C, Tsai KK, Hou M-F, Hung W-C. Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression. Breast Cancer Res 2014, 16:410.
267. Gerlini G, Di Gennaro P, Mariotti G, Urso C, Chiarugi A, Pimpinelli N, Borgognoni L. Indoleamine 2,3-dioxygenase + cells correspond to the BDCA2+ plasmacytoid dendritic cells in human melanoma sentinel nodes. J Invest Dermatol 2010, 130:898–901.
268. Munn DH, Sharma MD, Hou D, Baban B, Lee JR, Antonia SJ, Messina JL, Chandler P, Koni PA, Mellor AL. Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Investig 2004, 114:280–290.
269. Qian B, Deng Y, Im JH, Muschel RJ, Zou Y, Li J, Lang RA, Pollard JW. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One 2009, 4:e6562.
270. Geeraerts X, Bolli E, Fendt S-M, Van Ginderachter JA. Macrophage metabolism as therapeutic target for cancer, atherosclerosis, and obesity. Front Immunol 2017, 8:289.
271. Rodriguez PC, Quiceno DG, Zabaleta J, Ortiz B, Zea AH, Piazuelo MB, Delgado A, Correa P, Brayer J, Sotomayor EM, et al. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses. Cancer Res 2004, 64:5839–5849.
272. Rodriguez PC, Quiceno DG, Ochoa AC. L-Arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007, 109:1568–1573.
273. Bingisser RM, Tilbrook PA, Holt PG, Kees UR. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 1998, 160:5729–5734.
274. Harari O, Liao JK. Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des 2004, 10:893–898.
275. Rivoltini L, Carrabba M, Huber V, Castelli C, Novellino L, Dalerba P, Mortarini R, Arancia G, Anichini A, Fais S, et al. Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol Rev 2002, 188:97–113.
276. Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y, Fuhrer T, Kogadeeva M, Picotti P, Meissner F, Mann M, et al. L-Arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 2016, 167:829–842.e813.
277. Cao Y, Feng Y, Zhang Y, Zhu X, Jin F. L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo. BMC Cancer 2016, 16:343.
278. Nicholson B, Manner CK, Kleeman J, MacLeod CL. Sustained nitric oxide production in macrophages requires the arginine transporter CAT2. J Biol Chem 2001, 276:15881–15885.
279. Caso G, McNurlan MA, McMillan ND, Eremin O, Garlick PJ. Tumour cell growth in culture: dependence on arginine. Clin Sci 2004, 107:371–379.
280. Patil MD, Bhaumik J, Babykutty S, Banerjee UC, Fukumura D. Arginine dependence of tumor cells: targeting a chink in cancer's armor. Oncogene 2016, 35:4957–4972.
281. Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 2004, 172:989–999.
282. Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, Herber DL, Schneck J, Gabrilovich DI. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 2007, 13:828–835.
283. Srivastava MK, Sinha P, Clements VK, Rodriguez P, Ostrand-Rosenberg S. Myeloid-derived suppressor cells inhibit T cell activation by depleting cystine and cysteine. Cancer Res 2010, 70:68–77.
284. Pearce OMT, Läubli H, Verhagen A, Secrest P, Zhang J, Varki NM, Crocker PR, Bui JD, Varki A. Inverse hormesis of cancer growth mediated by narrow ranges of tumor-directed antibodies. Proc Natl Acad Sci USA 2014, 111:5998–6003.
285. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C. Molecular analysis of circulating tumour cells—biology and biomarkers. Nat Rev Clin Oncol 2014, 11:129–144.
286. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011, 11:85–95.
287. Faubert B, DeBerardinis RJ. Analyzing tumor metabolism in vivo. Annu Rev Cancer Biol 2017, 1:99–117.
288. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bäuerle T, Wallwiener M, et al. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 2013, 31:539–544.
289. Dharmasiri U, Njoroge SK, Witek MA, Adebiyi MG, Kamande JW, Hupert ML, Barany F, Soper SA. High-throughput selection, enumeration, electrokinetic manipulation, and molecular profiling of low-abundance circulating tumor cells using a microfluidic system. Anal Chem 2011, 83:2301–2309.
290. Demeulemeester J, Kumar P, Møller EK, Nord S, Wedge DC, Peterson A, Mathiesen RR, Fjelldal R, Zamani Esteki M, Theunis K, et al. Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing. Genome Biol 2016, 17:250.
291. Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 2013, 23:573–581.
292. Mathenge EG, Dean CA, Clements D, Vaghar-Kashani A, Photopoulos S, Coyle KM, Giacomantonio M, Malueth B, Nunokawa A, Jordan J, et al. Core needle biopsy of breast cancer tumors increases distant metastases in a mouse model. Neoplasia 2014, 16:950–960.
293. Robinson AJ, Brown AP. Tumour seeding in a case of malignant melanoma due to fine needle aspiration of a lymph node. J Plast Reconstr Aesthet Surg 2010, 63:e571–e572.
294. Shyamala K, Girish HC, Murgod S. Risk of tumor cell seeding through biopsy and aspiration cytology. J Int Soc Prevent Community Dent 2014, 4:5–11.
295. Duckwall CS, Murphy TA, Young JD. Mapping cancer cell metabolism with13C flux analysis: recent progress and future challenges. J Carcinog 2013, 12:13.
296. Zamboni N, Saghatelian A, Patti GJ. Defining the metabolome: ize, flux, and regulation. Mol Cell 2015, 58:699–706.
297. Nishiumi S, Suzuki M, Kobayashi T, Matsubara A, Azuma T, Yoshida M. Metabolomics for biomarker discovery in gastroenterological cancer. Metabolites 2014, 4:547–571.
298. Metallo CM, Heiden MGV. Understanding metabolic regulation and its influence on cell physiology. Mol Cell 2013, 49:388–398.
299. Domcke S, Sinha R, Levine DA, Sander C, Schultz N. Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun 2013, 4:2126.
300. Ertel A, Verghese A, Byers SW, Ochs M, Tozeren A. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells. Mol Cancer 2006, 5:55.
301. Gillet J-P, Calcagno AM, Varma S, Marino M, Green LJ, Vora MI, Patel C, Orina JN, Eliseeva TA, Singal V, et al. Redefining the relevance of established cancer cell lines to the study of mechanisms of clinical anti-cancer drug resistance. Proc Natl Acad Sci USA 2011, 108:18708–18713.
302. Vincent KM, Findlay SD, Postovit LM. Assessing breast cancer cell lines as tumour models by comparison of mRNA expression profiles. Breast Cancer Res 2015, 17:114.
303. Naipal KAT, Verkaik NS, Sánchez H, van Deurzen CHM, den Bakker MA, Hoeijmakers JHJ, Kanaar R, Vreeswijk MPG, Jager A, van Gent DC. Tumor slice culture system to assess drug response of primary breast cancer. BMC Cancer 2016, 16:78.
304. Fan TW-M, Lane AN, Higashi RM. Stable isotope resolved metabolomics studies in ex vivo tissue slices. Bio Protoc 2016, 6:e1730.
305. Bersini S, Jeon JS, Moretti M, Kamm RD. In vitro models of the metastatic cascade: from local invasion to extravasation. Drug Discov Today 2014, 19:735–742.
306. Buse MG. Hexosamines, insulin resistance and the complications of diabetes: current status. Am J Physiol Endocrinol Metab 2006, 290:E1–E8.
307. Ramanathan AA, Mehta A, Artlett CM. The impact of the unfolded protein response and the hexosamine biosynthetic pathway on glycosylation. Glycobiol Insights 2017, 6:1–12.
308. Schug ZT, Vande Voorde J, Gottlieb E. The metabolic fate of acetate in cancer. Nat Rev Cancer 2016, 16:708–717.