Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1983496 | The International Journal of Biochemistry & Cell Biology | 2015 | 15 Pages |
Abstract
The field of energy metabolism dramatically progressed in the last decade, owing to a large number of cancer studies, as well as fundamental investigations on related transcriptional networks and cellular interactions with the microenvironment. The concept of metabolic flexibility was clarified in studies showing the ability of cancer cells to remodel the biochemical pathways of energy transduction and linked anabolism in response to glucose, glutamine or oxygen deprivation. A clearer understanding of the large-scale bioenergetic impact of C-MYC, MYCN, KRAS and P53 was obtained, along with its modification during the course of tumor development. The metabolic dialog between different types of cancer cells, but also with the stroma, also complexified the understanding of bioenergetics and raised the concepts of metabolic symbiosis and reverse Warburg effect. Signaling studies revealed the role of respiratory chain-derived reactive oxygen species for metabolic remodeling and metastasis development. The discovery of oxidative tumors in human and mice models related to chemoresistance also changed the prevalent view of dysfunctional mitochondria in cancer cells. Likewise, the influence of energy metabolism-derived oncometabolites emerged as a new means of tumor genetic regulation. The knowledge obtained on the multi-site regulation of energy metabolism in tumors was translated to cancer preclinical studies, supported by genetic proof of concept studies targeting LDHA, HK2, PGAM1, or ACLY. Here, we review those different facets of metabolic remodeling in cancer, from its diversity in physiology and pathology, to the search of the genetic determinants, the microenvironmental regulators and pharmacological modulators.
Keywords
SCO2ANTETFGSEAMMTVTP53PDK1TIGARSREBPmTORCACLYATP citrate lyaseG6PPDHAMPKHNF4APGC1αHIF1αpspsUCPPKM2HK2LDHARHEBPGAM1ERRαF1,6BPpyruvate kinase M2 isoformEGFROXPHOSFADH2flavin adenine dinucleotideCOXPI3KGDHLKB1nuclear magnetic resonanceAMP-activated protein kinaseopa1PPARsROSAdenosine TriphosphateATPAktMetabolic flexibilityGOTGene Set Enrichment AnalysisGlutamic-oxaloacetic transaminaseadenine nucleotide translocatorNMRtumor protein p53KEGG یا Kyoto Encyclopedia of Genes and Genomes Kyoto Encyclopedia of Genes and GenomesRas homolog enriched in brainelectron transfer chainCancercytochrome c oxidasehypoxia inducible factor 1forkhead transcription factorFoxOphosphatase and tensin homologOxidative phosphorylationphosphoinositide 3-kinaseMitochondriaNADHnicotinamide dinucleotideMammalian target of rapamycin complexhexokinase 2ETcMouse mammary tumor virusoptic atrophy protein 1Uncoupling proteinprotein kinase Bpyruvate dehydrogenasePyruvate dehydrogenase kinase 1Ptenliver kinase B1Reactive oxygen speciesEstrogen-related receptor alphaEpidermal growth factor receptorPeroxisome proliferator-activated receptors
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Authors
Emilie Obre, Rodrigue Rossignol,