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

Research output: Contribution to journalArticle

Ahmad Fahim Ismail, Sevil Oskay Halacli, Nouf Babteen, Mario De Piano, Tracey A. Martin, Wen G. Jiang, Muhammad Shamim Khan, Prokar Dasgupta, Claire M. Wells

Original languageEnglish
Pages (from-to)1333-1346
JournalBiochemical Journal
Issue number8
Early online date23 Feb 2017
Publication statusPublished - 1 Apr 2017


King's Authors


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 datasets that PAK5mRNA levels are reduced in human bladder cancer compared to normal controls. Taken together this study proposes that PAK5 expression levels could be used as a novel prognostic marker for bladder cancer progression.

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