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 ORCID: https://orcid.org/0000-0003-2690-4908, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, 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

Preview

PDF - Accepted Post-Print Version Download (8MB) | Preview

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:	18 Nov 2024 05:30
URI:	https://orca.cardiff.ac.uk/id/eprint/98584

Citation Data

Cited 21 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item