Hsp27 regulates EGF/β-catenin mediated epithelial to mesenchymal transition in prostate cancer

Thomas Cordonnier, Jennifer L. Bishop, Masaki Shiota, Ka Mun Nip, Daksh Thaper, Sepideh Vahid, Devon Heroux, Martin Gleave, Amina Zoubeidi

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Increased expression of the molecular chaperone Hsp27 is associated with the progression of prostate cancer (PCa) to castration-resistant disease, which is lethal due to metastatic spread of the prostate tumor. Metastasis requires epithelial to mesenchymal transition (EMT), which endows cancer cells with the ability to disseminate from the primary tumor and colonize new tissue sites. A wide variety of secreted factors promote EMT, and while overexpression and constitutive activation of epidermal growth factor (EGF) signaling is associated with poor prognosis of PCa, a precise role of EGF in PCa progression to metastasis remains unclear. Here, we show that Hsp27 is required for EGF-induced cell migration, invasion and MMPs activity as well as the expression of EMT markers including Fibronectin, Vimentin and Slug with concomitant decrease of E-cadherin. Mechanistically, we found that Hsp27 is required for EGF-induced AKT and GSK3β phosphorylation and β-catenin nuclear translocation. Moreover, silencing Hsp27 decreases EGF dependent phosphorylation of β-catenin on tyrosine 142 and 654, enhances β-catenin ubiquitination and degradation, prevents β-catenin nuclear translocation and binding to the Slug promoter. These data suggest that Hsp27 is required for EGF-mediated EMT via modulation of the β-catenin/Slug signaling pathway. Together, our findings underscore the importance of Hsp27 in EGF induced EMT in PCa and highlight the use of Hsp27 knock-down as a useful strategy for patients with advanced disease.

Original languageEnglish
Pages (from-to)E496-E507
JournalInternational Journal of Cancer
Volume136
Issue number6
DOIs
Publication statusPublished - Mar 15 2015
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Hsp27 regulates EGF/β-catenin mediated epithelial to mesenchymal transition in prostate cancer'. Together they form a unique fingerprint.

Cite this