Secreted pyruvate kinase M2 facilitates cell migration via PI3K/Akt and Wnt/β-catenin pathway in colon cancer cells

Biochem Biophys Res Commun. 2015 Apr 3;459(2):327-332. doi: 10.1016/j.bbrc.2015.02.112. Epub 2015 Feb 28.

Abstract

Pyruvate Kinase M2 (PKM2) is a key glycolytic enzyme, which highly expressed in tumor cells, and plays a pivotal role in the growth, survival and metabolism reprogramming of cancer cells. Besides the location of cytoplasm as a glycolytic enzyme and the location of nucleus as a protein kinase, extracellular PKM2 is present in serum and feces of tumor patients. However, little is known about the secretion of PKM2 and its significance in the progression of colon cancer. Here we demonstrated that PKM2 could be secreted from colon cancer cells, and purified PKM2 protein mimicing the secreted PKM2 was able to promote colon cancer cell migration. Moreover, PI3K/Akt and Wnt/β-catenin signaling were involved in secreted PKM2 induced colon cancer cell migration. The results reveal critical roles of secreted PKM2 in the progression of colon cancer, and indicate that PKM2 may be a therapeutic target for colon cancer.

Keywords: Colon cancer; Migration; PKM1; PKM2; Secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Gene Knockdown Techniques
  • HCT116 Cells
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Pyruvate Kinase / antagonists & inhibitors
  • Pyruvate Kinase / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Wnt Signaling Pathway*
  • beta Catenin / antagonists & inhibitors
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • RNA, Small Interfering
  • beta Catenin
  • Phosphatidylinositol 3-Kinases
  • Pyruvate Kinase
  • Proto-Oncogene Proteins c-akt