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

Ismail, Ahmad Fahim, Oskay, Sevil, Babteen, Nouf, De Piano, Mario, Martin, Tracey Amanda, Jiang, Wen Guo, Khan, Muhammad, Dasgupta, Prokar and Wells, Claire M. 2017. PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells. Biochemical Journal 474 (8) , pp. 1333-1346. 10.1042/BCJ20160875

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: Portland Press
ISSN: 0264-6021
Funders: Cancer Research Wales
Date of First Compliant Deposit: 9 January 2018
Date of Acceptance: 21 February 2017
Last Modified: 24 Apr 2018 20:25
URI: http://orca.cf.ac.uk/id/eprint/98584

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