Pyruvate kinase M2 promotes the growth of gastric cancer cells via regulation of Bcl-xL expression at transcriptional level

Biochem Biophys Res Commun. 2012 Jun 22;423(1):38-44. doi: 10.1016/j.bbrc.2012.05.063. Epub 2012 May 22.

Abstract

PKM2 is an isoenzyme of the glycolytic enzyme pyruvate kinase that promotes aerobic glycolysis. Here, we describe an important role for PKM2 in regulating the survival of gastric cancer (GC) cells. We showed that PKM2 was overexpressed in gastric tumor tissues compared to normal tissues and its expression level was associated with poor survival of gastric cancer patients. We also showed that PKM2 affected cell survival by regulating Bcl-xL at the transcriptional level. PKM2 knockdown partially affected the stability of NF-kB subunit p65, suggesting that post-translational regulation of p65 by PKM2 is one of plausible mechanisms for the increased cell growth. Therefore, PKM2 may function as an upstream molecule that regulates p65 function and thus enhances the growth of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Prognosis
  • Pyruvate Kinase / genetics
  • Pyruvate Kinase / metabolism*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology*
  • Transcription Factor RelA / metabolism
  • Transcription, Genetic
  • bcl-X Protein / genetics*

Substances

  • BCL2L1 protein, human
  • Biomarkers, Tumor
  • Transcription Factor RelA
  • bcl-X Protein
  • Pyruvate Kinase