Related Experiment Video

Updated: May 25, 2025

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

13.2K

RhoB regulates prostate cancer cell proliferation and docetaxel sensitivity via the PI3K-AKT signaling pathway

Tiantian Sheng1, Hang Su2, Lu Yao3

  • 1Department of Pathology, Jining No.1 People's Hospital, Shandong First Medical University, Jining, 272000, Shandong, P.R. China.

BMC Cancer
|February 26, 2025
PubMed

Insights

RhoB protein is crucial for prostate cancer metastasis. Its absence increases docetaxel sensitivity but promotes cell migration, while its presence can lead to chemoresistance by activating the PI3K-AKT pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Docetaxel is a primary treatment for castration-resistant prostate cancer (CRPC).
  • RhoB GTPase influences prostate cancer metastasis by regulating cytoskeletal dynamics, cell migration, and focal adhesion.
  • The PI3K-AKT signaling pathway is implicated in prostate cancer progression.

Purpose of the Study:

  • To investigate the role of RhoB in prostate cancer metastasis and docetaxel response.
  • To elucidate the molecular mechanisms by which RhoB affects epithelial-mesenchymal transition (EMT) and chemoresistance.

Main Methods:

  • CRISPR/Cas9 gene editing was used to knock out the RhoB gene in PC-3 prostate cancer cells.
  • Gene editing efficiency was confirmed using T7 endonuclease I (T7EI) assays and Sanger sequencing.
  • RNA sequencing was performed on cells with RhoB knockout or overexpression to analyze pathway alterations.

Main Results:

  • RhoB knockout enhanced EMT and increased docetaxel sensitivity (decreased IC50) in PC-3 cells.
  • Loss of RhoB promoted prostate cancer cell migration and invasion, while RhoB overexpression reversed these effects.
  • RhoB regulates pathways including focal adhesion, ECM receptor interaction, and PI3K-AKT signaling, impacting EMT, migration, and invasion.
  • RhoB overexpression activated PI3K-AKT signaling under docetaxel treatment, potentially conferring chemoresistance.

Conclusions:

  • RhoB plays a dual role in prostate cancer, influencing metastasis and chemoresistance.
  • Targeting RhoB or associated pathways may offer new therapeutic strategies for CRPC.
  • RhoB's modulation of the PI3K-AKT pathway is a key mechanism for docetaxel resistance.
Keywords:
CRISPR/Cas9DocetaxelProstate cancerRNA-SeqRhoB

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