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RUNX1 positively regulates the ErbB2/HER2 signaling pathway through modulating SOS1 expression in gastric cancer

Yoshihide Mitsuda1, Ken Morita1, Gengo Kashiwazaki2

  • 1Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan.

Scientific Reports
|April 25, 2018
PubMed

Insights

Runt-related transcriptional factor 1 (RUNX1) regulates ErbB2/HER2 signaling in gastric cancer by activating SOS1. Inhibiting RUNX1 suppresses cancer cell proliferation, offering a new anti-tumor strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • The role of runt-related transcriptional factor 1 (RUNX1) in gastric cancer is unclear.
  • ErbB2/HER2 signaling is often upregulated in gastric cancer, promoting cancer cell survival.
  • Son of sevenless homolog (SOS) family proteins mediate receptor tyrosine kinase (RTK) cascades.

Purpose of the Study:

  • To investigate the role of RUNX1 in regulating the ErbB2/HER2 signaling pathway in gastric cancer.
  • To identify RUNX1 as a potential therapeutic target for gastric cancer treatment.

Main Methods:

  • Investigated RUNX1's regulation of SOS1 expression in gastric cancer cells.
  • Utilized RUNX1 knockdown and a novel RUNX inhibitor (Chb-M').
  • Assessed effects on ErbB2/HER2 signaling, SOS1 expression, and gastric cancer cell proliferation.

Main Results:

  • RUNX1 directly transactivates SOS1 expression by binding to its promoter.
  • RUNX1 knockdown decreased SOS1 expression and ErbB2/HER2 phosphorylation, suppressing proliferation.
  • The RUNX inhibitor Chb-M' deactivated ErbB2/HER2 signaling and inhibited gastric cancer cell lines.

Conclusions:

  • RUNX1 plays a critical role in maintaining ErbB2/HER2 signaling in gastric cancer.
  • Targeting RUNX1 or its downstream effectors like SOS1 presents a promising anti-tumor strategy.
  • This study uncovers a novel therapeutic avenue for gastric cancer management.

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