Genetically-defined metabolic reprogramming in cancer

Trends Endocrinol Metab. 2012 Nov;23(11):552-9. doi: 10.1016/j.tem.2012.06.009. Epub 2012 Jul 31.

Abstract

Oncogenes and tumor suppressors regulate cell metabolism. Evidence demonstrates that tumorigenic mutations in these genes tend to orchestrate metabolic activity into a platform that promotes cell survival, growth, and proliferation. Recent work has shown that some metabolic enzymes are also mutated in cancer, and that these mutations may influence malignancy directly. Thus, these enzymes seem to function as oncogenes and tumor suppressors, and would appear to be compelling targets for therapeutic intervention. Here, we review several enzymes mutated in cancer - phosphoglycerate dehydrogenase, isocitrate dehydrogenases 1 and 2, succinate dehydrogenase, and fumarate hydratase - and discuss exciting new work that has begun to pull back the curtain on how mutations in these enzymes influence tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / metabolism*
  • Fumarate Hydratase / genetics
  • Fumarate Hydratase / metabolism
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Phosphoglycerate Dehydrogenase / genetics
  • Phosphoglycerate Dehydrogenase / metabolism
  • Succinate Dehydrogenase / genetics
  • Succinate Dehydrogenase / metabolism

Substances

  • Isoenzymes
  • Mutant Proteins
  • Neoplasm Proteins
  • Isocitrate Dehydrogenase
  • Phosphoglycerate Dehydrogenase
  • Succinate Dehydrogenase
  • Fumarate Hydratase