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Updated: Feb 9, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

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Prostate-Derived Ets Factor (PDEF) Inhibits Metastasis by Inducing Epithelial/Luminal Phenotype in Prostate Cancer

Fengtian Wang1, Sweaty Koul2,3, Prakash S T Shanmugam1

  • 1Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana.

Molecular Cancer Research : MCR
|June 1, 2018
PubMed

Insights

Prostate cancer metastasis is inhibited by SPDEF/PDEF, which suppresses stemness and EMT via Twist1 and CK18. PDEF/Twist1 levels can predict lethal versus indolent prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Prostate cancer metastasis is a major cause of mortality.
  • Sam pointed domain ETS transcription factor (SPDEF/PDEF) inhibits prostate cancer metastasis, but the mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which PDEF inhibits prostate cancer metastasis.
  • To investigate the relationship between PDEF, Twist1, and cytokeratin 18 (CK18) in prostate cancer progression.
  • To evaluate the prognostic value of PDEF and Twist1 in prostate cancer patients.

Main Methods:

  • Microarray and gene set enrichment analysis to identify PDEF-regulated genes.
  • Analysis of the TRAMP mouse model for PDEF and Twist1 expression changes during cancer progression.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) to identify PDEF direct targets.
  • Knockdown experiments (Twist1 and CK18) to assess functional relationships.
  • Analysis of clinical prostate cancer cohorts.

Main Results:

  • PDEF upregulates epithelial differentiation genes and suppresses stemness and epithelial-to-mesenchymal transition (EMT) genes, notably Twist1.
  • PDEF expression is lost while Twist1 expression is gained during prostate cancer progression in TRAMP mice.
  • PDEF directly regulates CK18 transcription; CK18 knockdown increases Twist1 expression, indicating PDEF regulates Twist1 partly via CK18.
  • PDEF expression is inversely correlated with tumor grade, metastasis, and poor survival.
  • A PDEF/Twist1 signature predicts poor survival more effectively than either gene alone.

Conclusions:

  • PDEF inhibits prostate tumor progression and metastasis, partly through direct regulation of CK18, which in turn influences Twist1 expression.
  • The PDEF/Twist1 axis represents a novel mechanism in prostate cancer progression.
  • PDEF and Twist1 expression levels can serve as biomarkers to distinguish between lethal and indolent prostate cancer.

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