PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells

Lu Jiang1, Ting Lan, Yongchang Chen

  • 1Department of Physiology, School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.

Plos One
|April 25, 2013
PubMed
Abstract

Insights

Type II cGMP dependent protein kinase (PKG II) inhibits gastric cancer cell migration by blocking epidermal growth factor receptor (EGFR) activation. This PKG II action disrupts key signaling pathways, offering a potential therapeutic target for gastric cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Previous studies indicated Type II cGMP dependent protein kinase (PKG II) inhibits gastric cancer cell proliferation by blocking epidermal growth factor receptor (EGFR) and MAPK/ERK signaling.
  • This suggests PKG II may also inhibit other EGFR-triggered pathways and gastric cancer cell activities.

Purpose of the Study:

  • To investigate the inhibitory effect of PKG II on epidermal growth factor (EGF)/EGFR-induced migration in gastric cancer cells.
  • To identify the related signal transduction pathways involved in this inhibition.

Main Methods:

  • Gastric cancer cell line (AGS) was infected with Ad-PKG II and treated with 8-pCPT-cGMP to increase PKG II expression and activity.
  • Western Blotting and "Pull-down" assays were used to detect protein phosphorylation and small G protein activity (Ras, Rac1).
  • Cell migration was assessed using trans-well assays, and PKG II binding to EGFR was confirmed by Co-IP.

Main Results:

  • EGF stimulation increased AGS cell migration, involving PLCγ1 and ERK signaling pathways.
  • PKG II significantly inhibited EGF-induced migration and blocked EGF-initiated PLCγ1 and MAPK/ERK signaling.
  • This inhibition occurred by preventing EGF-induced phosphorylation of EGFR at Tyr 992 and Tyr 1068, with PKG II binding to EGFR and causing threonine phosphorylation.

Conclusions:

  • PKG II effectively inhibits EGF-induced migration and related PLCγ1 and MAPK/ERK signaling in gastric cancer cells.
  • PKG II exerts broad inhibition on EGF/EGFR signaling and biological activities.
  • PKG II phosphorylates EGFR, blocking its activation and thereby inhibiting gastric cancer cell migration.

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