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Extracellular PKM2 induces cancer proliferation by activating the EGFR signaling pathway

Ming-Chuan Hsu1, Wen-Chun Hung2, Hirohito Yamaguchi3

  • 1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer CenterHouston, TX, USA; National Institute of Cancer Research, National Health Research InstitutesTainan, Taiwan.

American Journal of Cancer Research
|May 7, 2016
PubMed

Insights

Secreted pyruvate kinase M2 (PKM2) promotes cancer cell proliferation by activating epidermal growth factor receptor (EGFR) signaling. This extracellular function of PKM2 offers new insights into cancer development and potential therapeutic targets.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Molecular Oncology

Background:

  • Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme implicated in cancer.
  • PKM2 exhibits functions beyond its enzymatic activity, crucial for cancer cell proliferation.
  • Dimeric PKM2 is detected in the circulation of cancer patients, suggesting an extracellular role.

Purpose of the Study:

  • To investigate the role of extracellular PKM2 in cancer progression.
  • To elucidate the mechanism by which secreted PKM2 influences cancer cell behavior.
  • To determine the relationship between PKM2, EGFR signaling, and cancer cell proliferation.

Main Methods:

  • Exposure of cells to recombinant PKM2 protein.
  • Knockdown of PKM2 expression.
  • Expression of a dimerization-prone PKM2 mutant (R399E).
  • Assessment of EGFR phosphorylation and downstream signaling activation.
  • Evaluation of cellular transformation and proliferation.

Main Results:

  • Recombinant PKM2 exposure increased EGFR phosphorylation.
  • Secreted PKM2 activated EGFR signaling and promoted proliferation in triple-negative breast cancer cells.
  • PKM2 knockdown reduced EGFR phosphorylation.
  • Dimeric PKM2 mutant enhanced EGFR phosphorylation, transformation, and proliferation more than wild-type PKM2.

Conclusions:

  • Extracellular PKM2 promotes cancer cell proliferation via EGFR activation.
  • Dimeric PKM2 plays a significant role in this process.
  • This study reveals a novel extracellular function of PKM2 in cancer, highlighting EGFR as a key mediator.
Keywords:
EGFRPKM2triple-negative breast cancer

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