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Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer
Journal article   Open access   Peer reviewed

Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer

Pooja G. Talati, Lei Gu, Elyse M. Ellsworth, Melanie A. Girondo, Marco Trerotola, David T. Hoang, Benjamin Leiby, Ayush Dagvadorj, Peter A. McCue, Costas D. Lallas, …
The American journal of pathology, v 185(9), pp 2505-2522
01 Sep 2015
DOI: https://doi.org/10.1016/j.ajpath.2015.04.026
PMID: 26362718
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1016/j.ajpath.2015.04.026View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Life Sciences & Biomedicine Pathology Science & Technology
Active Stat5a/b predicts early recurrence and disease-specific death in prostate cancer (PC), which both typically are caused by development of metastatic disease. Herein, we demonstrate that Stat5a/b induces epithelial-to-mesenchymal transition (EMT) of PC cells, as shown by Stat5a/b regulation of EMT marker expression (Twist1, E-cadherin, N-cadherin, vimentin, and fibronectin) in PC cell lines, xenograft tumors in vivo, and patient-derived PCs ex vivo using organ explant cultures. Jak2-Stat5a/b signaling induced functional end points of EMT as welt indicated by disruption of epithelial cell monolayers and increased migration and adhesion of PC cells to fibronectin. Knockdown of Twist1 suppressed Jak2-Stat5a/b induced EMT properties of PC cells, which were rescued by re-introduction of Twist1, indicating that Twist1 mediates Stat5a/b-induced EMT in PC cells. White promoting EMT, Jak2-Stat5a/b signaling induced stem-Like properties in PC cells, such as sphere formation and expression of cancer stem cell markers, including BMI1. Mechanistically, both Twist1 and BMI1 were critical for Stat5a/b induction of stem-like features, because genetic knockdown of Twist1 suppressed Stat5a/b-induced BMI1 expression and sphere formation in stem cell culture conditions, which were rescued by re-introduction of BMI1. By using human prolactin knock-in mice, we demonstrate that prolactin-Stat5a/b signaling promoted metastases formation of PC cells in vivo. In conclusion, our data support the concept that Jak2-Stat5a/b signaling promotes metastatic progression of PC by inducing EMT and stem cell properties in PC cells.

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60 citations in Web of Science
61 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Pathology
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