PKM2 Thr454 phosphorylation increases its nuclear translocation and promotes xenograft tumor growth in A549 human lung cancer cells

Biochem Biophys Res Commun. 2016 May 13;473(4):953-958. doi: 10.1016/j.bbrc.2016.03.160. Epub 2016 Apr 1.

Abstract

Pyruvate kinase M2 (PKM2) is a key enzyme of glycolysis which is highly expressed in many tumor cells, and plays an important role in the Warburg effect. In previous study, we found PIM2 phosphorylates PKM2 at Thr454 residue (Yu, etl 2013). However, the functions of PKM2 Thr454 modification in cancer cells still remain unclear. Here we find PKM2 translocates into the nucleus after Thr454 phosphorylation. Replacement of wild type PKM2 with a mutant (T454A) enhances mitochondrial respiration, decreases pentose phosphate pathway, and enhances chemosensitivity in A549 cells. In addition, the mutant (T454A) PKM2 reduces xenograft tumor growth in nude mice. These findings demonstrate that PKM2 T454 phosphorylation is a potential therapeutic target in lung cancer.

Keywords: Cancer; Glycolysis; Phosphorylation; Pyruvate kinase M2; Xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Active Transport, Cell Nucleus
  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Nucleus / metabolism*
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice, Nude
  • Mitochondria / metabolism
  • Pentose Phosphate Pathway
  • Phosphorylation
  • Pyruvate Kinase / chemistry
  • Pyruvate Kinase / metabolism*
  • Threonine / metabolism
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / chemistry
  • Thyroid Hormones / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Thyroid Hormones
  • Threonine
  • Pyruvate Kinase