Emerging concepts in bioenergetics and cancer research: Metabolic flexibility, coupling, symbiosis, switch, oxidative tumors, metabolic remodeling, signaling and bioenergetic therapy. (February 2015)

• Record Type: Journal Article
• Authors: Obre, Emilie; Rossignol, Rodrigue
• Is Part Of: International journal of biochemistry & cell biology. Volume 59(2015:Feb.)
• Page Start: 167
• Page End: 181
• Publication Date: 2015-02
• Subjects: ACLY ATP citrate lyase -- AKT protein kinase B -- ATP adenosine triphosphate -- ANT adenine nucleotide translocator -- AMPK AMP-activated protein kinase -- COX cytochrome c oxidase -- EGFR epidermal growth factor receptor -- ERRα estrogen-related receptor alpha -- ETC electron transfer chain -- ETF electron-flavo-protein -- FADH2 flavin adenine dinucleotide -- FOXO forkhead transcription factor -- F1, 6BP fructose1, 6-biphosphate -- GDH glutamine dehydrogenase -- GSEA Gene Set Enrichment Analysis -- GOT glutamic-oxaloacetic transaminase -- G6P glucose 6 phosphatex -- HIF1α hypoxia inducible factor 1 -- HK2 hexokinase 2 -- HNF4a hepatocyte nuclear growth factor a -- KEGG Kyoto Encyclopedia of Genes and Genomes -- LDHA lactate dehydrogenase isoform A -- LKB1 liver kinase B1 -- mTORC mammalian target of rapamycin complex -- MMTV Mouse mammary tumor virus -- NADH nicotinamide dinucleotide -- NMR nuclear magnetic resonance -- NSSN nutrient-sensing signaling network -- OXPHOS oxidative phosphorylation -- OPA1 optic atrophy protein 1 -- PGAM1 phosphoglyceric acid mutase -- PDH pyruvate dehydrogenase -- PGC1α peroxisome proliferator-activated receptor-gamma coactivator -- PKM2 pyruvate kinase M2 isoform -- PPARs peroxisome proliferator-activated receptors -- PSPs pathway switching proteins -- PDK1 pyruvate dehydrogenase kinase 1 -- PTEN phosphatase and TENsin homolog -- PI3K phosphoinositide 3-kinase -- RHEB Ras homolog enriched in brain -- ROS reactive oxygen species -- SREBP sterol regulatory element-binding transcription factor -- SCO2 cytochrome c oxidase assembly protein -- TIGAR TP53-inducible glycolysis and apoptosis regulator -- TP53 tumor protein p53 -- UCP uncoupling protein; Mitochondria -- Oxidative phosphorylation -- Cancer -- Metabolic flexibility -- Oncobioenergetics; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2014.12.008
• Languages: English
• ISSNs: 1357-2725

Abstract

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.