Metabolic effect of TAp63α: Enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense

Oncotarget

Volumn 5, Issue 17, 2014, Pages 7722-7733

  D'Alessandro, Angelo ^a,b   Amelio, Ivano ^c   Berkers, Celia R ^d,e   Antonov, Alexey ^c   Vousden, Karen H ^d   Melino, Gerry ^c,f,g   Zolla, Lello ^a  

^a UNIVERSITY OF TUSCIA   (Italy)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF LEICESTER   (United Kingdom)

^d BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

^e UTRECHT UNIVERSITY   (Netherlands)

^f UNIVERSITY OF ROME TOR VERGATA   (Italy)

^g CNR   (Italy)

Author keywords

Glutaminolysis; Glycolysis; Metabolomics; P53 family; p63

Indexed keywords

6 PHOSPHOGLUCONATE; CARBOHYDRATES AND CARBOHYDRATE DERIVATIVES; CARBON 13; DOXYCYCLINE; GLUCOSE; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; GLUTAMINE; GLUTATHIONE DISULFIDE; HEXOSE PHOSPHATE; MESSENGER RNA; N TERMINAL TRANSACTIVATION DOMAIN P63 ALPHA; PALMITIC ACID; PHOSPHOGLUCONATE DEHYDROGENASE; PROTEIN P53; PYRUVIC ACID; RIBOSE PHOSPHATE; SEDOHEPTULOSE 7 PHOSPHATE; SERINE; UNCLASSIFIED DRUG; TP63 PROTEIN, HUMAN; TRANSCRIPTION FACTOR; TUMOR SUPPRESSOR PROTEIN;

ANTIOXIDANT DEFENSE; ARTICLE; BIOINFORMATICS; CANCER METABOLISM; CANCER PROGNOSIS; CANCER SURVIVAL; CARBOXYLATION; CATABOLISM; CELLULAR DISTRIBUTION; CELLULAR, SUBCELLULAR AND MOLECULAR BIOLOGICAL PHENOMENA AND FUNCTIONS; CITRIC ACID CYCLE; COMPARATIVE STUDY; CONTROLLED STUDY; FATTY ACID SYNTHESIS; G1 PHASE CELL CYCLE CHECKPOINT; GENE EXPRESSION; GLYCOLYSIS; HOMEOSTASIS; HUMAN; HUMAN CELL; INCUBATION TIME; ISOTOPE LABELING; MALIGNANT NEOPLASTIC DISEASE; METABOLIC FLUX ANALYSIS; METABOLIC REGULATION; METABOLISM; METABOLOMICS; MOLECULAR DYNAMICS; NUCLEOTIDE METABOLISM; OXIDATIVE STRESS; PENTOSE PHOSPHATE CYCLE; PEPTIDE SYNTHESIS; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEOMICS; SAOS 2 CELL LINE; SURVIVAL RATE; SURVIVAL TIME; BIOLOGY; FLOW CYTOMETRY; IMMUNOBLOTTING; NEOPLASM; PHYSIOLOGY; TUMOR CELL LINE;

CELL LINE, TUMOR; COMPUTATIONAL BIOLOGY; FLOW CYTOMETRY; GLYCOLYSIS; HUMANS; IMMUNOBLOTTING; METABOLOMICS; NEOPLASMS; OXIDATIVE STRESS; PENTOSE PHOSPHATE PATHWAY; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS;

EID: 84907484052     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.2300     Document Type: Article

References (42)

1. Warburg O. On the origin of cancer cells. Science 1956; 123:309-314
2. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324:1029-1033
3. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144(5):646-674
4. Markert EK, Levine AJ, Vazquez A. Proliferation and tissue remodeling in cancer: the hallmarks revisited. Cell Death Dis. 2012; 3:e397.
5. Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 2012; 21:297-308
6. Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev. 2009; 23(5):537-548
7. Levine AJ, Puzio-Kuter AM. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 2010; 330(6009):1340-1344
8. D'Alessandro A, Zolla L. Proteomics and metabolomics in cancer drug development. Expert Rev Proteomics. 2013; 10(5):473-488
9. Berkers CR, Maddocks OD, Cheung EC, Mor I, Vousden KH. Metabolic Regulation by p53 Family Members. Cell. Metab. 2013; 18(5):617-633
10. Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell 2009; 137:413-431
11. Melino G, Lu X, Gasco M, Crook T, Knight RA. Functional regulation of p73 and p63: development and cancer. Trends Biochem Sci. 2003; 28(12):663-670
12. Murray-Zmijewski F, Lane DP, Bourdon JC. p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006; 13(6):962-972
13. Maddocks OD, Berkers CR, Mason SM, Zheng L, Blyth K, Gottlieb E, Vousden KH. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature. 2013; 493(7433):542-546
14. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F and Hwang PM. p53 regulates mitochondrial respiration. Science. 2006; 312(5780):1650-1653.
15. Bensaad K, Cheung EC and Vousden KH. Modulation of intracellular ROS levels by TIGAR controls autophagy. EMBO J. 2009; 28(19):3015-3026.
16. Hu W, Zhang C, Wu R, Sun Y, Levine A and Feng Z. Glutaminase 2, a novel p53 target gene regulating energy metabolism and antioxidant function. Proc Natl Acad Sci U S A. 2010; 107(16):7455-7460.
17. Suzuki S, Tanaka T, Poyurovsky MV, Nagano H, Mayama T, Ohkubo S, Lokshin M, Hosokawa H, Nakayama T, Suzuki Y, Sugano S, Sato E, Nagao T, Yokote K, Tatsuno I and Prives C. Phosphate-activated glutaminase (GLS2), a p53-inducible regulator of glutamine metabolism and reactive oxygen species. Proc Natl Acad Sci U S A. 2010; 107(16):7461-7466.
18. Gogna R, Madan E, Kuppusamy P and Pati U. Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications. Cell death & disease. 2012; 3:e286.
19. Sanchez-Macedo N, Feng J, Faubert B, Chang N, Elia A, Rushing EJ, Tsuchihara K, Bungard D, Berger SL, Jones RG, Mak TW and Zaugg K. Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model. Cell Death Differ. 2013; 20(4):659-668.
20. Zaugg K, Yao Y, Reilly PT, Kannan K, Kiarash R, Mason J, Huang P, Sawyer SK, Fuerth B, Faubert B, Kalliomaki T, Elia A, Luo X, Nadeem V, Bungard D, Yalavarthi S, et al. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress. Genes Dev. 2011; 25(10):1041-1051.
21. Bergeaud M, Mathieu L, Guillaume A, Moll UM, Mignotte B, Le Floch N, Vayssiere JL and Rincheval V. Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F(1)F0-ATP synthase. Cell Cycle. 2013; 12(17):2781-2793.
22. Rufini A, Niklison-Chirou MV, Inoue S, Tomasini R, Harris IS, Marino A, et al. TAp73 depletion accelerates aging through metabolic dysregulation. Genes Dev. 2012; 26(18):2009-2014
23. D'Alessandro A, Marrocco C, Rinalducci S, Peschiaroli A, Timperio AM, Bongiorno-Borbone L, et al. Analysis of TAp73-dependent signaling via Omics technologies. J. Proteome Res. 2013; 12(9):4207-4220
24. Amelio I, Markert EK, Rufini A, Antonov A, Sayan BS, Tucci P, et al. P73 regulates serine biosynthesis in cancer. Oncogene 2013; doi:10.1038/onc.2013.456
25. D'Aguanno S, Barcaroli D, Rossi C, Zucchelli M, Ciavardelli D, Cortese C, De Cola A, Volpe S, D'Agostino D, Todaro M, Stassi G, Di Ilio C, Urbani A, De Laurenzi V. p63 isoforms regulate metabolism of cancer stem cells. J Proteome Res. 2014;13(4):2120-36.
26. Su X, Gi YJ, Chakravarti D, Chan IL, Zhang A, Xia X, et al. TAp63 is a master transcriptional regulator of lipid and glucose metabolism. Cell Metab. 2012; 16(4):511-525
27. Gressner O, Schilling T, Lorenz K, Schulze Schleithoff E, Koch A, Schulze-Bergkamen H, et al. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria. EMBO J. 2005;24(13):2458-2471
28. DeBerardinis RJ, Mancuso A, Daikhin E, Nissim I, Yudkoff M,Wehrli S, et al. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci USA 2007; 104:19345-19350
29. Anastasiou D, Cantley LC. Breathless cancer cells get fat on glutamine. Cell Res. 2012; 22(3):443-446
30. Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ, et al. p63 regulates glutaminase 2 expression. Cell Cycle 2013; 12(9):1395-1405
31. Amelio I, Cutruzzola F, Antonov A, Agostini M and Melino G. Serine and glycine metabolism in cancer. Trends Biochem Sci. 2014; 39(4):191-198
32. Chaneton B, Hillmann P, Zheng L, Martin AC, Maddocks OD, Chokkathukalam A, Coyle JE, Jankevics A, Holding FP, Vousden KH, Frezza C, O'Reilly M and Gottlieb E. Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature. 2012; 491(7424):458-462
33. Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011; 476(7360):346-350.
34. Tedeschi PM, Markert EK, Gounder M, Lin H, Dvorzhinski D, Dolfi SC, Chan LL, Qiu J, DiPaola RS, Hirshfield KM, Boros LG, Bertino JR, Oltvai ZN and Vazquez A. Contribution of serine, folate and glycine metabolism to the ATP, NADPH and purine requirements of cancer cells. Cell death & disease. 2013; 4:e877.
35. Frezza C and Gottlieb E. Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol. 2009; 19(1):4-11
36. Giacobbe A, Bongiorno-Borbone L, Bernassola F, Terrinoni A, Markert EK, Levine AJ, Feng Z, Agostini M, Zolla L, Agro AF, Notterman DA, Melino G and Peschiaroli A. p63 regulates glutaminase 2 expression. Cell Cycle. 2013; 12(9):1395-1405
37. Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, Yang Y, Linehan WM, Chandel NS and DeBerardinis RJ. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 2012; 481(7381):385-388.
38. Fan J, Kamphorst JJ, Rabinowitz JD and Shlomi T. Fatty acid labeling from glutamine in hypoxia can be explained by isotope exchange without net reductive isocitrate dehydrogenase (IDH) flux. The Journal of biological chemistry. 2013; 288(43):31363-31369.
39. Lyssiotis CA, Vander-Heiden MG, Munoz-Pinedo C and Emerling BM. Emerging concepts: linking hypoxic signaling and cancer metabolism. Cell death & disease. 2012; 3:e303.
40. Heikal AA. Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies. Biomark Med. 2010; 4(2):241-263
41. Chiarugi A, Dolle C, Felici R and Ziegler M. The NAD metabolome-a key determinant of cancer cell biology. Nat Rev Cancer. 2012; 12(11):741-752
42. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature. 2012; 486(7403):346-352