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.
PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells
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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; PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells. Biochem J 15 April 2017; 474 (8): 1333–1346. doi: https://doi.org/10.1042/BCJ20160875
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