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DOCK1 regulates the malignant biological behavior of endometrial cancer through c-Raf/ERK pathway

Shangdan Xie1, Yanshan Jin1, Jiakun Wang2

  • 1Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, Zhejiang, China.

BMC Cancer
|March 4, 2024
PubMed
Abstract

Insights

The DOCK1 gene promotes endometrial cancer progression by enhancing cell viability, proliferation, and invasion. Its effects are mediated through the c-RAF/ERK1/2 signaling pathway, offering potential therapeutic targets for endometrial carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of the DOCK1 gene in endometrial carcinoma's biological behavior and associated pathways remains largely unexplored.
  • Understanding DOCK1's function is crucial for developing targeted therapies for endometrial cancer.

Purpose of the Study:

  • To investigate the effect of the DOCK1 gene on the biological behavior of endometrial carcinoma cells.
  • To elucidate the underlying molecular mechanisms, including the c-RAF/ERK1/2 signaling pathway.

Main Methods:

  • Immunohistochemistry and Western blot for DOCK1 protein expression analysis.
  • Cell viability, proliferation, invasion, migration, and apoptosis assays (CCK-8, BrdU, Transwell, flow cytometry).
  • In vivo xenograft models to assess DOCK1's effect on tumor growth.

Main Results:

  • DOCK1 expression is significantly upregulated in endometrial cancer tissues and cells.
  • DOCK1 knockout inhibited, while overexpression enhanced, malignant cellular behaviors (viability, proliferation, invasion).
  • DOCK1 modulates the expression of key proteins (E-cadherin, MMP9, Bcl-2, Ezrin) and the c-RAF/ERK1/2 pathway, with observed effects in vivo.

Conclusions:

  • DOCK1 enhances the malignant biological behavior of endometrial cancer cells.
  • The c-RAF/ERK1/2 signaling pathway is implicated in DOCK1's oncogenic function.
  • DOCK1 represents a potential therapeutic target for endometrial carcinoma.
Keywords:
DOCK1ERKEndometrial cancerMechanismc-Raf

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