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Updated: Aug 14, 2025

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Increased endogenous PKG I activity attenuates EGF-induced proliferation and migration of epithelial ovarian cancer

Ting Lan1,2, Ying Li3, Yue Wang2

  • 1Xuzhou Key Laboratory of Laboratory Diagnostics, Xuzhou Medical University, Xuzhou City, Jiangsu Province, China.

Cell Death & Disease
|January 18, 2023
PubMed

Insights

Activating protein kinase I (PKG I) suppresses epithelial ovarian cancer (EOC) growth by inhibiting EGF signaling. This PKG I activation disrupts the EGFR pathway, offering a potential therapeutic target for EOC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The tumor suppressor role of type I cGMP-dependent protein kinase (PKG I) is established, but its function in EGFR-driven epithelial ovarian cancer (EOC) is not fully understood.
  • EGFR signaling is implicated in EOC progression, yet the interplay with PKG I remains unclear.

Purpose of the Study:

  • To investigate the effects of activated PKG I on EGF-induced EOC cell proliferation, migration, and invasion.
  • To elucidate the molecular mechanisms underlying PKG I's action in EOC, focusing on its interaction with the EGFR pathway.

Main Methods:

  • In vitro studies using EOC cell lines treated with 8-Br-cGMP (a PKG I activator).
  • In vivo studies utilizing an EOC xenograft nude mouse model.
  • Analysis of EGFR and downstream signaling pathway components (e.g., p-EGFR, SOS1, Grb2, c-Raf, MEK1/2, ERK1/2) phosphorylation levels.

Main Results:

  • Activated PKG I significantly attenuated EGF-induced EOC cell proliferation, migration, and invasion in vitro and in vivo.
  • PKG I activation led to increased threonine (693) and decreased tyrosine (1068) phosphorylation of EGFR.
  • This modulation disrupted the EGFR-SOS1-Grb2 complex, reduced downstream MEK/ERK phosphorylation, and inhibited ERK nuclear translocation.

Conclusions:

  • Activation of PKG I effectively suppresses EGF-induced EOC progression.
  • The 8-Br-cGMP-PKG I-EGFR/MEK/ERK signaling axis represents a promising therapeutic target for epithelial ovarian cancer treatment.

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