Document Type
Article
Publication Date
6-10-2015
Abstract
In this study, we show that the transmembrane glycoprotein Trop-2 is up-regulated in human prostate cancer (PCa) with extracapsular extension (stages pT3/pT4) as compared to organ-confined (stage pT2) PCa. Consistent with this evidence, Trop-2 expression is found to be increased in metastatic prostate tumors of Transgenic Adenocarcinoma of Mouse Prostate mice and to strongly correlate with α5β1 integrin levels. Using PCa cells, we show that Trop-2 specifically associates with the α5 integrin subunit, as binding to α3 is not observed, and that Trop-2 displaces focal adhesion kinase from focal contacts. In support of the role of Trop-2 as a promoter of PCa metastatic phenotype, we observe high expression of this molecule in exosomes purified from Trop-2-positive PCa cells. These vesicles are then found to promote migration of Trop-2-negative PCa cells on fibronectin, an α5β1 integrin/focal adhesion kinase substrate, thus suggesting that the biological function of Trop-2 may be propagated to recipient cells. In summary, our findings show that Trop-2 promotes an α5β1 integrin-dependent pro-metastatic signaling pathway in PCa cells and that the altered expression of Trop-2 may be utilized for early identification of capsule-invading PCa.
Recommended Citation
Trerotola, Marco; Ganguly, Kirat K; Fazli, Ladan; Fedele, Carmine; Lu, Huimin; Dutta, Anindita; Liu, Qin; De Angelis, Tiziana; Riddell, Luke W; Riobo, Natalia A; Gleave, Martin E; Zoubeidi, Amina; Pestell, Richard; Altieri, Dario C; and Languino, Lucia R, "Trop-2 is up-regulated in invasive prostate cancer and displaces FAK from focal contacts." (2015). Department of Urology Faculty Papers. Paper 28.
https://jdc.jefferson.edu/urologyfp/28
PubMed ID
26015409
Comments
This article has been peer reviewed. It was published in: Oncotarget.
Volume 6, Issue 16, 2015, Pages 14318-14328.
The published version is available at http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3960&path[]=8612
Copyright © 2015 The Authors