p53 and metabolism: From mechanism to therapeutics

Imagem de Miniatura
Arquivos
art_SIMABUCO_p53_and_metabolism_From_mechanism_to_therapeutics_2018.PDF (3.64 MB)
Citações na Scopus
98
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
IMPACT JOURNALS LLC
Autores
SIMABUCO, F. M.
PAVAN, I. C. B.
MORELLI, A. P.
SILVA, F. R.
Citação
ONCOTARGET, v.9, n.34, p.23780-23823, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
The tumor cell changes itself and its microenvironment to adapt to different situations, including action of drugs and other agents targeting tumor control. Therefore, metabolism plays an important role in the activation of survival mechanisms to keep the cell proliferative potential. The Warburg effect directs the cellular metabolism towards an aerobic glycolytic pathway, despite the fact that it generates less adenosine triphosphate than oxidative phosphorylation; because it creates the building blocks necessary for cell proliferation. The transcription factor p53 is the master tumor suppressor; it binds to more than 4,000 sites in the genome and regulates the expression of more than 500 genes. Among these genes are important regulators of metabolism, affecting glucose, lipids and amino acids metabolism, oxidative phosphorylation, reactive oxygen species (ROS) generation and growth factors signaling. Wild-type and mutant p53 may have opposing effects in the expression of these metabolic genes. Therefore, depending on the p53 status of the cell, drugs that target metabolism may have different outcomes and metabolism may modulate drug resistance. Conversely, induction of p53 expression may regulate differently the tumor cell metabolism, inducing senescence, autophagy and apoptosis, which are dependent on the regulation of the PI3K/AKT/mTOR pathway and/or ROS induction. The interplay between p53 and metabolism is essential in the decision of cell fate and for cancer therapeutics. © Simabuco et al.
Palavras-chave
Chemotherapy, Drug resistance, Metabolism, Mutant p53, P53
URI
https://observatorio.fm.usp.br/handle/OPI/31056
Referências
  1. Hanahan, D., Weinberg, R.A., The hallmarks of cancer (2000) Cell, 100, pp. 57-70. , https://doi.org/10.1016/S0092-8674(00)81683-9
  2. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation (2011) Cell, 144, pp. 646-674. , https://doi.org/10.1016/j.cell.2011.02.013
  3. Warburg, O., Wind, F., Negelein, E., The metabolism of tumors in the body (1927) J Gen Physiol, 8, pp. 519-530. , https://doi.org/10.1085/jgp.8.6.519.PMID:19872213
  4. Cantor, J.R., Sabatini, D.M., Cancer cell metabolism: one hallmark, many faces (2012) Cancer Discov, 2, pp. 881-898. , https://doi.org/10.1158/2159-8290.CD-12-0345
  5. Jadvar, H., Alavi, A., Gambhir, S.S., 18F-FDG uptake in lung, breast, and colon cancers: molecular biology correlates and disease characterization (2009) J Nucl Med, 50, pp. 1820-1827. , https://doi.org/10.2967/jnumed.108.054098
  6. DeBerardinis, R.J., Lum, J.J., Hatzivassiliou, G., Thompson, C.B., The biology of cancer: metabolic reprogramming fuels cell growth and proliferation (2008) Cell Metab, 7, pp. 11-20. , https://doi.org/10.1016/j.cmet.2007.10.002
  7. Vander Heiden, M.G., Cantley, L.C., Thompson, C.B., Understanding the Warburg effect: the metabolic requirements of cell proliferation (2009) Science, 324, pp. 1029-1033. , https://doi.org/10.1126/science.1160809
  8. Lu, H., Forbes, R.A., Verma, A., Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis (2002) J Biol Chem, 277, pp. 23111-23115. , https://doi.org/10.1074/jbc.M202487200
  9. Estrella, V., Chen, T., Lloyd, M., Wojtkowiak, J., Cornnell, H.H., Ibrahim-Hashim, A., Bailey, K., Gillies, R.J., Acidity generated by the tumor microenvironment drives local invasion (2013) Cancer Res, 73, pp. 1524-1535. , https://doi.org/10.1158/0008-5472.CAN-12-2796
  10. Calcinotto, A., Filipazzi, P., Grioni, M., Iero, M., De Milito, A., Ricupito, A., Cova, A., Generoso, L., Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes (2012) Cancer Res, 72, pp. 2746-2756. , https://doi.org/10.1158/0008-5472.CAN-11-1272
  11. Brand, K.A., Hermfisse, U., Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species (1997) FASEB J, 11, pp. 388-395
  12. Ruckenstuhl, C., Büttner, S., Carmona-Gutierrez, D., Eisenberg, T., Kroemer, G., Sigrist, S.J., Fröhlich, K.U., Madeo, F., The Warburg effect suppresses oxidative stress induced apoptosis in a yeast model for cancer (2009) PLoS One, 4. , https://doi.org/10.1371/journal.pone.0004592
  13. Newsholme, E.A., Crabtree, B., Ardawi, M.S., The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells (1985) Biosci Rep, 5, pp. 393-400. , https://doi.org/10.1007/BF01116556
  14. Reitzer, L.J., Wice, B.M., Kennell, D., Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells (1979) J Biol Chem, 254, pp. 2669-2676
  15. DeBerardinis, R.J., Mancuso, A., Daikhin, E., Nissim, I., Yudkoff, M., Wehrli, S., Thompson, C.B., Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis (2007) Proc Natl Acad Sci USA, 104, pp. 19345-19350. , https://doi.org/10.1073/pnas.0709747104
  16. Vaughn, A.E., Deshmukh, M., Glucose metabolism inhibits apoptosis in neurons and cancer cells by redox inactivation of cytochrome c (2008) Nat Cell Biol, 10, pp. 1477-1483. , https://doi.org/10.1038/ncb1807
  17. Anastasiou, D., Cantley, L.C., Breathless cancer cells get fat on glutamine (2012) Cell Res, 22, pp. 443-446. , https://doi.org/10.1038/cr.2012.5
  18. Mazurek, S., Boschek, C.B., Hugo, F., Eigenbrodt, E., Pyruvate kinase type M2 and its role in tumor growth and spreading (2005) Semin Cancer Biol, 15, pp. 300-308. , https://doi.org/10.1016/j.semcancer.2005.04.009
  19. Zwerschke, W., Mazurek, S., Massimi, P., Banks, L., Eigenbrodt, E., Jansen-Dürr, P., Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein (1999) Proc Natl Acad Sci USA, 96, pp. 1291-1296. , https://doi.org/10.1073/pnas.96.4.1291
  20. Christofk, H.R., Vander Heiden, M.G., Wu, N., Asara, J.M., Cantley, L.C., Pyruvate kinase M2 is a phosphotyrosinebinding protein (2008) Nature, 452, pp. 181-186. , https://doi.org/10.1038/nature06667
  21. Cairns, R.A., Harris, I.S., Mak, T.W., Regulation of cancer cell metabolism (2011) Nat Rev Cancer, 11, pp. 85-95. , https://doi.org/10.1038/nrc2981
  22. Ye, J., Mancuso, A., Tong, X., Ward, P.S., Fan, J., Rabinowitz, J.D., Thompson, C.B., Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation (2012) Proc Natl Acad Sci USA, 109, pp. 6904-6909. , https://doi.org/10.1073/pnas.1204176109
  23. Maddocks, O.D., Berkers, C.R., Mason, S.M., Zheng, L., Blyth, K., Gottlieb, E., Vousden, K.H., Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells (2013) Nature, 493, pp. 542-546. , https://doi.org/10.1038/nature11743
  24. Labuschagne, C.F., van den Broek, N.J., Mackay, G.M., Vousden, K.H., Maddocks, O.D., Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells (2014) Cell Reports, 7, pp. 1248-1258. , https://doi.org/10.1016/j.celrep.2014.04.045
  25. Locasale, J.W., Grassian, A.R., Melman, T., Lyssiotis, C.A., Mattaini, K.R., Bass, A.J., Heffron, G., Mullarky, E., Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis (2011) Nat Genet, 43, pp. 869-874. , https://doi.org/10.1038/ng.890
  26. Possemato, R., Marks, K.M., Shaul, Y.D., Pacold, M.E., Kim, D., Birsoy, K., Sethumadhavan, S., Stransky, N., Functional genomics reveal that the serine synthesis pathway is essential in breast cancer (2011) Nature, 476, pp. 346-350. , https://doi.org/10.1038/nature10350
  27. Amelio, I., Cutruzzolá, F., Antonov, A., Agostini, M., Melino, G., Serine and glycine metabolism in cancer (2014) Trends Biochem Sci, 39, pp. 191-198. , https://doi.org/10.1016/j.tibs.2014.02.004
  28. Nilsson, R., Jain, M., Madhusudhan, N., Sheppard, N.G., Strittmatter, L., Kampf, C., Huang, J., Mootha, V.K., Metabolic enzyme expression highlights a key role for MTHFD2 and the mitochondrial folate pathway in cancer (2014) Nat Commun, 5, p. 3128. , https://doi.org/10.1038/ncomms4128
  29. Liu, Y., Borchert, G.L., Donald, S.P., Diwan, B.A., Anver, M., Phang, J.M., Proline oxidase functions as a mitochondrial tumor suppressor in human cancers (2009) Cancer Res, 69, pp. 6414-6422. , https://doi.org/10.1158/0008-5472.CAN-09-1223
  30. Kress, M., May, E., Cassingena, R., May, P., Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum (1979) J Virol, 31, pp. 472-483
  31. Lane, D.P., Crawford, L.V., T antigen is bound to a host protein in SV40-transformed cells (1979) Nature, 278, pp. 261-263. , https://doi.org/10.1038/278261a0
  32. Linzer, D.I., Levine, A.J., Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells (1979) Cell, 17, pp. 43-52. , https://doi.org/10.1016/0092-8674(79)90293-9

Coleções
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03