p53 and metabolism: From mechanism to therapeutics

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorSIMABUCO, F. M.
dc.contributor.authorMORALE, M. G.
dc.contributor.authorPAVAN, I. C. B.
dc.contributor.authorMORELLI, A. P.
dc.contributor.authorSILVA, F. R.
dc.contributor.authorTAMURA, R. E.
dc.date.accessioned2019-03-13T17:12:37Z
dc.date.available2019-03-13T17:12:37Z
dc.date.issued2018
dc.description.abstractThe 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.eng
dc.description.indexPubMedeng
dc.identifier.citationONCOTARGET, v.9, n.34, p.23780-23823, 2018
dc.identifier.doi10.18632/oncotarget.25267
dc.identifier.issn1949-2553
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/31056
dc.language.isoeng
dc.publisherIMPACT JOURNALS LLCeng
dc.relation.ispartofOncotarget
dc.rightsopenAccesseng
dc.rights.holderCopyright IMPACT JOURNALS LLCeng
dc.subjectChemotherapyeng
dc.subjectDrug resistanceeng
dc.subjectMetabolismeng
dc.subjectMutant p53eng
dc.subjectP53eng
dc.subject.otherantineoplastic agenteng
dc.subject.othercerulenineng
dc.subject.othergrowth factoreng
dc.subject.othermammalian target of rapamycineng
dc.subject.otheroxythiamineeng
dc.subject.otherphosphatidylinositol 3 kinaseeng
dc.subject.otherprotein kinase beng
dc.subject.otherprotein mdm2eng
dc.subject.otherprotein p53eng
dc.subject.otherreactive oxygen metaboliteeng
dc.subject.otherresveratroleng
dc.subject.otherritonavireng
dc.subject.othertetrahydrolipstatineng
dc.subject.othertln 232eng
dc.subject.otherunclassified drugeng
dc.subject.otheraerobic glycolysiseng
dc.subject.otheramino acid metabolismeng
dc.subject.otherapoptosiseng
dc.subject.otherautophagyeng
dc.subject.othercell fateeng
dc.subject.othercell growtheng
dc.subject.othercell metabolismeng
dc.subject.othercitric acid cycleeng
dc.subject.otherdrug targetingeng
dc.subject.otherenzyme regulationeng
dc.subject.othergene expression regulationeng
dc.subject.otherglucose metabolismeng
dc.subject.otherhumaneng
dc.subject.otherintracellular signalingeng
dc.subject.otherionizing radiationeng
dc.subject.otherkidney metastasiseng
dc.subject.otherlipid metabolismeng
dc.subject.otherliver cancereng
dc.subject.othermalignant neoplasmeng
dc.subject.othermelanomaeng
dc.subject.othermetabolic regulationeng
dc.subject.othermetabolismeng
dc.subject.othermyelomaeng
dc.subject.otherosteosarcomaeng
dc.subject.otheroxidative phosphorylationeng
dc.subject.otherprotein dna bindingeng
dc.subject.otherprotein functioneng
dc.subject.otherprotein metabolismeng
dc.subject.otherprotein phosphorylationeng
dc.subject.otherrevieweng
dc.subject.othersenescenceeng
dc.subject.otherthyroid cancereng
dc.subject.othertranscription regulationeng
dc.subject.othertumor microenvironmenteng
dc.titlep53 and metabolism: From mechanism to therapeuticseng
dc.typearticleeng
dc.type.categoryrevieweng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalSIMABUCO, F. M.:Laboratory of Functional Properties in Foods, School of Applied Sciences (FCA), Universidade de Campinas (UNICAMP), Limeira, São Paulo, Brazil
hcfmusp.author.externalPAVAN, I. C. B.:Laboratory of Functional Properties in Foods, School of Applied Sciences (FCA), Universidade de Campinas (UNICAMP), Limeira, São Paulo, Brazil
hcfmusp.author.externalMORELLI, A. P.:Laboratory of Functional Properties in Foods, School of Applied Sciences (FCA), Universidade de Campinas (UNICAMP), Limeira, São Paulo, Brazil
hcfmusp.author.externalSILVA, F. R.:Laboratory of Functional Properties in Foods, School of Applied Sciences (FCA), Universidade de Campinas (UNICAMP), Limeira, São Paulo, Brazil
hcfmusp.citation.scopus99
hcfmusp.contributor.author-fmusphcMIRIAN GALLIOTE MORALE
hcfmusp.contributor.author-fmusphcRODRIGO ESAKI TAMURA
hcfmusp.description.beginpage23780
hcfmusp.description.endpage23823
hcfmusp.description.issue34
hcfmusp.description.volume9
hcfmusp.origemSCOPUS
hcfmusp.origem.pubmed29805774
hcfmusp.origem.scopus2-s2.0-85046706242
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