Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay

Cancer Research

Volumn 72, Issue 19, 2012, Pages 5130-5140

  Fiaschi, Tania ^a   Marini, Alberto ^a   Giannoni, Elisa ^a   Taddei, Maria Letizia ^a   Gandellini, Paolo ^c   De Donatis, Alina ^a   Lanciotti, Michele ^b   Serni, Sergio ^b   Cirri, Paolo ^a   Chiarugi, Paola ^a  

^a ISTITUTO TOSCANO TUMORI   (Italy)

^b UNIVERSITY OF FLORENCE   (Italy)

^c NATIONAL CANCER INSTITUTE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR; LACTIC ACID; MONOCARBOXYLATE TRANSPORTER 1; MONOCARBOXYLATE TRANSPORTER 4; SIRTUIN 3;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER ASSOCIATED FIBROBLAST; CANCER CELL; CELL METABOLISM; CELL PROLIFERATION; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENSITOMETRY; DOWN REGULATION; FIBROBLAST; GLUCOSE INTAKE; HUMAN; HUMAN CELL; HUMAN TISSUE; MALE; MOUSE; NONHUMAN; NUCLEAR REPROGRAMMING; OXIDATION REDUCTION POTENTIAL; PHENOTYPE; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN SYNTHESIS;

ANIMALS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELLS, CULTURED; FIBROBLASTS; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE; GLUCOSE TRANSPORTER TYPE 1; GLYCOLYSIS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1; LACTIC ACID; MALE; MICE; MICE, SCID; MITOCHONDRIA; MODELS, BIOLOGICAL; MONOCARBOXYLIC ACID TRANSPORTERS; MUSCLE PROTEINS; NEOPLASMS, EXPERIMENTAL; OXIDATIVE STRESS; PROSTATIC NEOPLASMS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SIRTUIN 3; TRANSPLANTATION, HETEROLOGOUS;

EID: 84867112200     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-12-1949     Document Type: Article

References (46)

1. Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003;3:453-8. (Pubitemid 37328849)
2. Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Nat Rev Cancer 2009;9:239-52.
3. Cirri P, Chiarugi P. Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer Metastasis Rev 2012;31:195-208.
4. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009;119:1420-8.
5. Mueller MM, Fusenig NE. Friends or foes - bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 2004;4:839-49. (Pubitemid 39472951)
6. Mantovani A, Germano G, Marchesi F, Locatelli M, Biswas SK. Cancer-promoting tumor-associated macrophages: new vistas and open questions. Eur J Immunol 2011;41:2522-5.
7. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011;144:646-74.
8. Koppenol WH, Bounds PL, Dang CV. Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer 2011;11:325-37.
9. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
10. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 2008;452:230-3. (Pubitemid 351380249)
11. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, et al. Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 2010;329:1492-9.
12. Sonveaux P, Vegran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, et al. Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008;118:3930-42.
13. Finley LW, Carracedo A, Lee J, Souza A, Egia A, Zhang J, et al. SIRT3 opposes reprogramming of cancer cell metabolismthrough HIF1alpha destabilization. Cancer Cell 2011;19:416-28.
14. Anastasiou D, Poulogiannis G, Asara JM, Boxer MB, Jiang JK, Shen M, et al. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 2011;334:1278-83.
15. Gruning NM, Ralser M. Cancer: sacrifice for survival. Nature 2011;480:190-1.
16. Gruning NM, Rinnerthaler M, Bluemlein K, Mulleder M, Wamelink MM, Lehrach H, et al. Pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells. Cell Metab 2011;14:415-27.
17. Giannoni E, Bianchini F, Calorini L, Chiarugi P. Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal 2011;14:2361-71.
18. Giannoni E, Bianchini F, Masieri L, Serni S, Torre E, Calorini L, et al. Reciprocal activation of prostate cancer cells and cancer-associated fibroblasts stimulates epithelial-mesenchymal transition and cancer stemness. Cancer Res 2010;70:6945-56.
19. Cat B, Stuhlmann D, Steinbrenner H, Alili L, Holtkotter O, Sies H, et al. Enhancement of tumor invasion depends on transdifferentiation of skin fibroblasts mediated by reactive oxygen species. J Cell Sci 2006;119:2727-38. (Pubitemid 44184009)
20. Laberge RM, Awad P, Campisi J, Desprez PY. Epithelial-mesenchymal transition induced by senescent fibroblasts. Cancer Microenviron 2012;5:39-44.
21. Toullec A, Gerald D, Despouy G, Bourachot B, Cardon M, Lefort S, et al. Oxidative stress promotes myofibroblast differentiation and tumour spreading. EMBO Mol Med 2010;2:211-30.
22. Koukourakis MI, Giatromanolaki A, Harris AL, Sivridis E.Comparison of metabolic pathways between cancer cells and stromal cells in colorectal carcinomas: a metabolic survival role for tumor-associated stroma. Cancer Res 2006;66:632-7. (Pubitemid 43165922)
23. Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz AK, Frank PG, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle 2009;8:3984-4001.
24. Lisanti MP, Martinez-Outschoorn UE, Chiavarina B, Pavlides S, Whitaker-Menezes D, Tsirigos A, et al. Understanding the "lethal" drivers of tumor-stroma co-evolution: emerging role(s) for hypoxia, oxidative stress and autophagy/mitophagy in the tumor micro-environment. Cancer Biol Ther 2010;10:537-42.
25. Bell EL, Emerling BM, Ricoult SJ, Guarente L. SIRT3 suppresses hypoxia inducible factor 1alpha and tumor growth by inhibiting mitochondrial ROS production. Oncogene 2011;30:2986-96.
26. Chen Y, Zhang J, Lin Y, Lei Q, Guan KL, Zhao S, et al. Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS. EMBO Rep 2011;12:534-41.
27. Colen CB, Shen Y, Ghoddoussi F, Yu P, Francis TB, Koch BJ, et al. Metabolic targeting of lactate efflux by malignant glioma inhibits invasiveness and induces necrosis: an in vivo study. Neoplasia 2011;13:620-32.
28. Cimen H, Han MJ, Yang Y, Tong Q, Koc H, Koc EC. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 2010;49:304-11.
29. Lisanti MP, Martinez-Outschoorn UE, Lin Z, Pavlides S, Whitaker-Menezes D, Pestell RG, et al. Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer". Cell Cycle 2011;10:2440-9.
30. Pavlides S, Vera I, Gandara R, Sneddon S, Pestell RG, Mercier I, et al. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid Redox Signal 2012;16:1264-84.
31. Rattigan YI, Patel BB, Ackerstaff E, Sukenick G, Koutcher JA, Glod JW, et al. Lactate is a mediator of metabolic cooperation between stromal carcinoma associated fibroblasts and glycolytic tumor cells in the tumor microenvironment. Exp Cell Res 2012;318:326-35.
32. Witkiewicz AK, Whitaker-Menezes D, Dasgupta A, Philp NJ, Lin Z, Gandara R, et al. Using the "reverse Warburg effect" to identify high-risk breast cancer patients: stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers. Cell Cycle 2012;11:1108-17.
33. Balliet RM, Capparelli C, Guido C, Pestell TG, Martinez-Outschoorn UE, Lin Z, et al. Mitochondrial oxidative stress in cancer-associated fibroblasts drives lactate production, promoting breast cancer tumor growth: understanding the aging and cancer connection. Cell Cycle 2011;10:4065-73.
34. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B, et al. Ketones and lactate "fuel" tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010;9:3506-14.
35. Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer. Cancer Res 2011;71:6921-5.
36. Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, Ertel A, Flomenberg N, Witkiewicz AK, et al. Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle 2011;10:1772-83.
37. Boidot R, Vegran F, Meulle A, Le BA, Dessy C, Sonveaux P, et al. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors. Cancer Res 2012;72:939-48.
38. Giannoni E, Parri M, Chiarugi P. EMT and oxidative stress: a bidirectional interplay affecting tumor malignancy. Antioxid Redox Signal 2012;16:1248-63.
39. Pani G, Giannoni E, Galeotti T, Chiarugi P. Redox-based escape mechanism from death: the cancer lesson. Antioxid Redox Signal 2009;11:2791-806.
40. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, et al. Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the "reverse Warburg effect": a transcriptional informatics analysis with validation. Cell Cycle 2010;9:2201-19.
41. Schumacker PT. SIRT3 controls cancer metabolic reprogramming by regulating ROS and HIF. Cancer Cell 2011;19:299-300.
42. Zhang DD. The Nrf2-Keap1-ARE signaling pathway: the regulation and dual function of Nrf2 in cancer. Antioxid Redox Signal 2010;13:1623-6.
43. Iqbal MA, Bamezai RN. Resveratrol inhibits cancer cell metabolism by down regulating pyruvate kinase M2via inhibition of mammalian target of rapamycin. PLoS One 2012;7:e36764.
44. Perl A, Hanczko R, Telarico T, Oaks Z, Landas S. Oxidative stress, inflammation and carcinogenesis are controlled through the pentose phosphate pathway by transaldolase. Trends Mol Med 2011;17:395-403.
45. Polimeni M, Voena C, Kopecka J, Riganti C, Pescarmona G, Bosia A, et al. Modulation of doxorubicin resistance by the glucose-6-phosphate dehydrogenase activity. Biochem J 2011;439:141-9.
46. Ying H, Kimmelman AC, Lyssiotis CA, Hua S, Chu GC, Fletcher-Sananikone E, et al. Oncogenic kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 2012;149:656-70.