title: PAK5 mediates cell: cell adhesion integrity via interaction with E-cadherin in bladder cancer cells.
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.
authors.affiliation: Division of Cancer Studies, King's College London, Rm.2.34A New Hunts House, Guy's Campus, London SE1 1UL, U.K.|Universiti Teknologi MARA, Shah Alam, Malaysia.
authors.forename: Ahmad Fahim
authors.initials: AF
authors.lastname: Ismail
authors.affiliation: Division of Cancer Studies, King's College London, Rm.2.34A New Hunts House, Guy's Campus, London SE1 1UL, U.K.
authors.forename: Sevil
authors.initials: S
authors.lastname: Oskay Halacli
authors.affiliation: Division of Cancer Studies, King's College London, Rm.2.34A New Hunts House, Guy's Campus, London SE1 1UL, U.K.
authors.forename: Nouf
authors.initials: N
authors.lastname: Babteen
authors.affiliation: Division of Cancer Studies, King's College London, Rm.2.34A New Hunts House, Guy's Campus, London SE1 1UL, U.K.
authors.forename: Mario
authors.initials: M
authors.lastname: De Piano
authors.affiliation: Cardiff University, Cardiff CF14 4XN, U.K.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Martin
authors.affiliation: Cardiff University, Cardiff CF14 4XN, U.K.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: MRC Centre of Transplantation and Biomedical Research Centre King's College London, Guy's Hospital, London, U.K.
authors.forename: Muhammad Shamim
authors.initials: MS
authors.lastname: Khan
authors.affiliation: MRC Centre of Transplantation and Biomedical Research Centre King's College London, Guy's Hospital, London, U.K.
authors.forename: Prokar
authors.initials: P
authors.lastname: Dasgupta
authors.affiliation: Division of Cancer Studies, King's College London, Rm.2.34A New Hunts House, Guy's Campus, London SE1 1UL, U.K. claire.wells@kcl.ac.uk.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Wells
mesh_terms: D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007365:Intercellular Junctions / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D001743:Urinary Bladder / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D054462:p21-Activated Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C443802:PAK5 protein, human; D054462:p21-Activated Kinases
keywords: E-cadherin; bladder; p21-activated kinase 5