MP21-09 PLECTIN-1 DEPLETION IN MUSCLE INVASIVE BLADDER CANCER CELL LINES PROMOTES PHOSPHORYLATION OF FER TYROSINE KINASE AND ENHANCES INVASION POTENTIAL

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research I1 Apr 2014MP21-09 PLECTIN-1 DEPLETION IN MUSCLE INVASIVE BLADDER CANCER CELL LINES PROMOTES PHOSPHORYLATION OF FER TYROSINE KINASE AND ENHANCES INVASION POTENTIAL Hiromichi Iwamura, Tohru Yoneyama, Yuki Tobisawa, Shingo Hatakeyama, Takuya Koie, and Chikara Ohyama Hiromichi IwamuraHiromichi Iwamura More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Yuki TobisawaYuki Tobisawa More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Takuya KoieTakuya Koie More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.837AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Plectin-1 which acts as a cytoskeletal crosslinker protein affects mechanical as well as dynamic properties of cytoskeleton. It was reported that Plectin-1 directly bind to Fer tyrosine kinase (Fer) and suppress phosphorylation of Fer and downstream signaling in mouse fibroblasts [Lunter et al., BBRC: 296, 904-910, 2002]. Plectin-1 is often impaired in muscle invasive bladder cancer [Okusa et al., J Electrophoresis: 52, 19-23, 2008], yet roles and underlying mechanisms of plectin-1 and Fer in bladder cancer progression remain unclear. Here, we investigated the role of plectin-1 and Fer in bladder cancer cell lines. METHODS We used the 2 bladder cancer cell lines YTS-1 (muscle invasive) and RT4 (superficial). Expression of plectin-1 and Fer in bladder cancer cells was analyzed by immunofluorescence (IF) staining and immunoblotting (IB). Interaction of plectin-1 and Fer in bladder cancer cells was analyzed by immunoprecipitation (IP). Bladder cancer cells were tested for invasion potential against basal membrane extract (BME) gel or bladder smooth muscle cell (BdSMC) monolayer. We also examined the role of Fer in invasion capacity using Fer knockdown YTS-1 cells. Furthermore, we examined expression of phospho-Fer in bladder cancer tissues. RESULTS IB and IF staining showed that expression of plectin-1 was much higher in RT4 compared with YTS-1. Although the expression of Fer was decreased in YTS-1, expression of phosphor-Fer was much higher in YTS-1 compared with RT4. Phosphorylation of ERK or AKT which is a downstream signaling molecules of Fer was also up-regulated in YTS-1. IP showed that plectin-1 bound to Fer in RT4 but not bound to Fer in YTS-1. In YTS-1, Fer was bound to vimentin. Invasion capacity against BME gel and BdSMC in YTS-1 was much higher than those of RT4. Immunohistochemical analyses of bladder cancer tissues showed that the upregulation of phospho-Fer correlated with poor prognosis of bladder cancer. CONCLUSIONS These results indicate that plectin-1 depletion in muscle invasive bladder cancer cells promotes phosphorylation of Fer and enhances invasion capacity. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e228-e229 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hiromichi Iwamura More articles by this author Tohru Yoneyama More articles by this author Yuki Tobisawa More articles by this author Shingo Hatakeyama More articles by this author Takuya Koie More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...