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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation

Wei Lv1, Mengxi Huan1, Wenjie Yang1

  • 1Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.

Biochemical and Biophysical Research Communications
|August 2, 2020
PubMed

Insights

Prostate cancer (PCa) metastasis is accelerated by Snail, which causes Speckle-type pox virus and zinc finger protein (SPOP) degradation. This post-translational regulation of SPOP promotes PCa cell migration and AKT pathway activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Prostate cancer (PCa) is a leading cause of cancer mortality in men.
  • Speckle-type pox virus and zinc finger protein (SPOP) is the most frequently mutated gene in PCa and acts as a tumor suppressor.
  • The upstream regulation of SPOP in PCa metastasis is not well understood.

Purpose of the Study:

  • To investigate the role of SPOP regulation in prostate cancer metastasis.
  • To elucidate the mechanism by which SPOP is degraded in metastatic PCa cells.

Main Methods:

  • Utilized a Snail-induced metastatic PCa mouse model.
  • Investigated protein degradation pathways and molecular interactions.
  • Analyzed the role of the SPOP BTB domain in Snail-mediated degradation.

Main Results:

  • Observed accelerated SPOP protein degradation in metastatic PCa cells.
  • Demonstrated that Snail binding induces SPOP ubiquitination and degradation.
  • Identified the SPOP BTB domain as critical for Snail-mediated degradation.
  • Linked SPOP degradation to PCa cell migration and AKT pathway activation.

Conclusions:

  • Snail promotes PCa metastasis by inducing SPOP degradation at a post-translational level.
  • This regulation involves SPOP ubiquitination and is dependent on the SPOP BTB domain.
  • Findings reveal a novel mechanism facilitating PCa cell migration and AKT pathway activation.
Keywords:
MigrationProstate cancerSPOPSnail

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