Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer

Trends Biochem Sci. 2012 Aug;37(8):309-16. doi: 10.1016/j.tibs.2012.04.003. Epub 2012 May 23.

Abstract

Cancer cell metabolism is exemplified by high glucose consumption and lactate production. Pyruvate kinase (PK), which catalyzes the final step of glycolysis, has emerged as a potential regulator of this metabolic phenotype. The M2 isoform of PK (PKM2) is highly expressed in cancer cells. However, the mechanisms by which PKM2 coordinates high energy requirements with high anabolic activities to support cancer cell proliferation are still not completely understood. Current research has elucidated novel regulatory mechanisms for PKM2, contributing to its important role in cancer. This review summarizes the current understanding and explores future directions in the field, highlighting controversies regarding the activity and specificity of PKM2 in cancer. In light of this knowledge, the potential therapeutic implications and strategies are critically discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Enzyme Activation
  • Gene Expression Regulation, Neoplastic*
  • Glycolysis*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Phosphorylation
  • Reactive Oxygen Species / metabolism
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Carrier Proteins
  • Isoenzymes
  • Membrane Proteins
  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Thyroid Hormones
  • Transcription Factors
  • thyroid hormone-binding proteins