From bioenergetics to the metabolic regulation of carcinogenesis

Author: R. Rossignol
Submitted: Thursday 10th of February 2011 10:11:54 AM
Submitted by: egf
Language: English
Content type: Learning resource
Educational levels: expert, qc3

Abstract

In this course, we discuss the concept of variable metabolic remodeling and signaling in tumors, specifically the modifications in the main biochemical energy pathways observed in cultured cancer cells and excised tumors, as well as the concentration changes in various (onco)metabolites that participate in the regulation of gene expression in cancer cells. In particular, pyruvate, oxaloacetate, succinate and fumarate, four mitochondrial metabolites, activate genes relevant for tumor progression. When the balance between glycolysis and oxidative phosphorylation is altered, these metabolites accumulate in the cytoplasm and regulate the activity of the Hypoxia Inducible Factor 1alpha (HIF-1alpha). HIF is one of the main factors that orchestrate the metabolic switch observed during oncogenesis. There is also an important role for lactate, fructose 1-6 bisphosphate or citrate that leads to the diversion of glucose metabolites to anabolism. In addition reactive oxygen species, which are produced by the respiratory chain, could serve as an endogenous source of DNA-damaging agents to promote genetic instability. Accordingly, several mitochondrial DNA mutations were reported in tumors, and the construction of cybrids recently demonstrated their role in the control of tumor progression. An important point of this lecutre will be the dramatic variability of the metabolic profile observed between tumors, and their ongoing modulation during carcinogenesis by oncogene activation and changes in tumor microenvironmental conditions.

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Original version - English

abstract rossignol_5122.pdf

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Citation

R. Rossignol. From bioenergetics to the metabolic regulation of carcinogenesis. EUROGENE portal. February 2011. online: http://eurogene.open.ac.uk/content/bioenergetics-metabolic-regulation-carcinogenesis

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