Related Experiment Video

Updated: Jan 10, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Effect of TGF-β mediated phenotypic changes on prostate cancer cell anoikis response

Prerna R Nepali1, Edgar Gonzalez-Kozlova2,3, Maitri Anegondi4

  • 1Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Oncogene
|November 22, 2025
PubMed

Insights

Prostate cancer cells undergoing epithelial mesenchymal transition (EMT) become vulnerable to anoikis (cell death). Targeting this EMT-anoikis vulnerability with DZ-50 may overcome therapy resistance in lethal prostate cancer.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Epithelial mesenchymal transition (EMT) promotes prostate cancer metastasis and therapy resistance by circumventing anoikis.
  • Understanding the regulation of EMT-MET (mesenchymal epithelial transition) interconversions by TGF-β is crucial for targeting prostate cancer progression.

Purpose of the Study:

  • To investigate how TGF-β regulates EMT-MET phenotypic interconversions to enhance anoikis response in pre-clinical prostate cancer models.
  • To assess the effect of EMT priming on anoikis vulnerability when treated with antitumor agents.

Main Methods:

  • Utilized human prostate cancer cell line models with varying responses to TGF-β and antitumor agents.
  • Assessed cellular response to TGF-β (EMT inducer) and antitumor agents (DZ-50 and cabazitaxel).
  • Analyzed phenotypic changes, anoikis vulnerability, and molecular markers (pSRC, cofilin).

Main Results:

  • TGF-β induced EMT in LNCaPTβRII cells and apoptosis in VCaP cells.
  • EMT-primed LNCaPTβRII cells exhibited anoikis vulnerability, characterized by downregulation of pSRC and cofilin.
  • Metabolic changes were observed at the EMT-anoikis intersection in LNCaPTβRII cells.
  • DZ-50 overcame cabazitaxel resistance in C4-2B TaxR cells and improved treatment response in cells and castration-resistant organoids.

Conclusions:

  • Prostate cancer cells programmed for EMT become vulnerable to anoikis-mediated cell death.
  • Exploiting the EMT-anoikis intersection offers potential for overcoming taxane chemotherapy resistance in lethal prostate cancer.
  • DZ-50 demonstrates potential in sensitizing prostate cancer cells to anoikis and overcoming therapeutic resistance.

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