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A novel function of hepatocyte growth factor in the activation of checkpoint kinase 1 phosphorylation in colon cancer

Na Song1,2, Xiaofang Che1,2, Lu Xu1,2

  • 1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 110001, People's Republic of China.

Molecular and Cellular Biochemistry
|June 3, 2017
PubMed

Insights

Hepatocyte growth factor (HGF) activates checkpoint kinase 1 (Chk1) phosphorylation in colon cancer cells via AKT signaling. This pathway involves TopBP1 and RAD51, impacting cancer prognosis and therapy.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The ATR/checkpoint kinase 1 (Chk1) pathway is crucial for DNA damage response and homologous recombination.
  • Chk1 phosphorylation influences cancer prognosis and therapeutic resistance.
  • Receptor tyrosine kinases regulate Chk1 phosphorylation, but HGF's role is unknown.

Purpose of the Study:

  • To investigate the effect of hepatocyte growth factor (HGF) on Chk1 phosphorylation in colon cancer cells.
  • To elucidate the role of AKT signaling in mediating HGF-induced Chk1 activation.
  • To determine the impact of HGF on TopBP1, RAD51, and TopBP1-ATR complex formation.

Main Methods:

  • Utilized colon cancer cell lines.
  • Assessed HGF-induced Chk1 phosphorylation.
  • Investigated the role of AKT signaling by depleting AKT activity and using AKT inhibitors.
  • Examined the expression of TopBP1 and RAD51.
  • Analyzed TopBP1-ATR complex formation.

Main Results:

  • HGF moderately activated Chk1 phosphorylation in colon cancer cells.
  • HGF upregulated TopBP1 and RAD51, promoting TopBP1-ATR complex formation.
  • HGF-activated AKT signaling mediated HGF-induced Chk1 phosphorylation.
  • AKT activity regulated TopBP1 and RAD51 expression.
  • AKT inhibition attenuated basal p-Chk1 and HGF-induced Chk1 activation.

Conclusions:

  • HGF regulates Chk1 phosphorylation in colon cancer cells.
  • AKT signaling is a key mediator linking HGF/MET signaling to Chk1 phosphorylation.
  • These findings suggest potential therapeutic strategies for managing cancer prognosis and sensitivity.
Keywords:
AKTChk1Colon cancerHGFMET

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