PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells.
Biochem J
; 474(8): 1333-1346, 2017 Mar 24.
Article
in En
| MEDLINE
| ID: mdl-28232500
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 cellcell 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 cellcell junctions and the level of PAK5 expression. Interestingly, exogenous PAK5 has recently been described to be associated with cellcell 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder
/
Urinary Bladder Neoplasms
/
Cadherins
/
Gene Expression Regulation, Neoplastic
/
P21-Activated Kinases
/
Intercellular Junctions
/
Neoplasm Proteins
Type of study:
Prognostic_studies
Language:
En
Journal:
Biochem J
Year:
2017
Document type:
Article
Affiliation country:
Reino Unido