The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer

Yibin Pan1,2, Jiena Zhou1,2,3, Weidan Zhang1,2,4

  • 1Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.

Cancer Medicine
|June 2, 2021
PubMed
Abstract

Insights

In epithelial ovarian cancer, Sonic Hedgehog (SHH) pathway is upregulated, promoting cell migration. Inhibiting SHH and autophagy may offer a new therapeutic strategy for ovarian cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Sonic Hedgehog (SHH) signaling pathway is implicated in human cancers, but its precise role in ovarian cancer remains unclear.
  • Understanding SHH pathway mechanisms is crucial for developing targeted ovarian cancer therapies.

Purpose of the Study:

  • To investigate the role of the SHH signaling pathway and autophagy in epithelial ovarian cancer (EOC).
  • To explore the therapeutic potential of inhibiting the SHH pathway and autophagy in EOC.

Main Methods:

  • Expression analysis of SHH and SQSTM1 in ovarian tumor tissues.
  • In vitro and in vivo experiments using SHH inhibitor (Cyclopamine) and autophagy inhibitor (chloroquine).
  • Assays included autophagic flux, cell viability (CCK-8), migration (wound healing, Transwell), and tumor xenografts. Mechanistic studies utilized qRT-PCR and Western Blot.

Main Results:

  • SHH and SQSTM1/P62 were upregulated in epithelial ovarian cancer tissues.
  • Cyclopamine induced autophagy via the PI3K/AKT pathway.
  • Combined low-dose Cyclopamine and chloroquine enhanced SKOV3 cell migration.

Conclusions:

  • SHH pathway inhibition and autophagy modulation show promise as a therapeutic strategy for ovarian cancer.
  • Targeting both SHH signaling and autophagy may represent a novel approach for EOC treatment.

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