Pyruvate kinase M2 in blood circulation facilitates tumor growth by promoting angiogenesis

J Biol Chem. 2014 Sep 12;289(37):25812-21. doi: 10.1074/jbc.M114.576934. Epub 2014 Jul 28.

Abstract

It is long known that pyruvate kinase isoform M2 (PKM2) is released into the circulation of cancer patients. The PKM2 levels in patients have been suggested as a diagnostic marker for many types of cancers. However, it is not known how PKM2 is released in the blood, and whether the circulating PKM2 has any physiological function(s) in tumor progression. In this report, we demonstrate that PKM2 in the blood facilitates tumor growth by promoting tumor angiogenesis. Our experiments show that PKM2 promotes tumor angiogenesis by increasing endothelial cell proliferation, migration, and cell-ECM adhesion. Only the dimeric PKM2 possess the activity in promoting tumor angiogenesis, which is consistent with the observations that PKM2 in circulation of cancer patients is a dimer form.

Keywords: Angiogenesis; Cell Adhesion; Cell Migration; Endothelial Cell; Glycolysis; Pyruvate Kinase.

Publication types

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

MeSH terms

  • Animals
  • Carrier Proteins / blood*
  • Cell Adhesion / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Glycolysis / genetics
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Membrane Proteins / blood*
  • Mice
  • Neoplasms / blood
  • Neoplasms / pathology
  • Neoplastic Cells, Circulating / metabolism
  • Neovascularization, Pathologic / blood
  • Neovascularization, Pathologic / pathology*
  • Protein Isoforms / blood*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / blood*
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Protein Isoforms
  • Thyroid Hormones