PAK5 mediates cell: Cell adhesion integrity via interaction with E-cadherin in bladder cancer cells

• Published in: Biochemical Journal
• Main Author: Ismail A.F.; Halacli S.O.; Babteen N.; De Piano M.; Martin T.A.; Jiang W.G.; Khan M.S.; Dasgupta P.; Wells C.M.
• Format: Article
• Language: English
• Published: Portland Press Ltd 2017
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018517633&doi=10.1042%2fBCJ20160875&partnerID=40&md5=f38d45881d2be0059753d175da81a10a

Urothelial bladder cancer is a major cause of morbidity and mortality worldwide, causing an estimated 150 000 deaths per year. Whilst non-muscle-invasive bladder tumours can be effectively treated, with high survival rates, many tumours recur, and some will progress to muscle-invasive disease with a much poorer long-term prognosis. Thus, there is a pressing need to understand the molecular transitions occurring within the progression of bladder cancer to an invasive disease. Tumour invasion is often associated with a down-regulation of E-cadherin expression concomitant with a suppression of cell:cell junctions, and decreased levels of E-cadherin expression have been reported in higher grade urothelial bladder tumours. We find that expression of E-cadherin in a panel of bladder cancer cell lines correlated with the presence of cell:cell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cell:cell junctions and we now find that endogenous PAK5 is localised to cell junctions and interacts with an E-cadherin complex. Moreover, depletion of PAK5 expression significantly reduced junctional integrity. These data suggest a role for PAK5 in maintaining junctional stability and we find that, in both our own patient samples and a commercially available dataset, PAK5mRNA levels are reduced in human bladder cancer compared with normal controls. Taken together, the present study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression. © 2017 The Author(s).