title: Tumour-promoting activity of altered WWP1 expression in breast cancer and its utility as a prognostic indicator.
abstract: WWP1 is a ubiquitin ligase, associated with the post-translational regulation of several tumour-promoting and tumour suppressor proteins. Here we show that WWP1 expression is up-regulated in a subset of breast tumour cell lines and primary breast tumours. We overexpressed WWP1 in MCF10A breast epithelial cells and demonstrated increased cell growth and anchorage-independent colony formation. RNAi knockdown of WWP1 expression in T47D and MCF7 breast tumour cell lines reduced anchorage-independent colony formation. We used WWP1 protein expression levels, in combination with its sub-cellular localization, to classify breast tumours into four categories. Surprisingly, a category with low/absent WWP1 expression displayed a consistently worse prognosis compared with WWP1-expressing tumours. Importantly, the association with disease-free survival was independent of the status of other commonly used prognostic indicators. Thus, WWP1 is a prognostic marker and may be a potential therapeutic target for a subset of breast tumours.
authors.affiliation: University of Manchester, Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: N S
authors.initials: NS
authors.lastname: Nguyen Huu
authors.forename: W D J
authors.initials: WD
authors.lastname: Ryder
authors.forename: N
authors.initials: N
authors.lastname: Zeps
authors.forename: M
authors.initials: M
authors.lastname: Flasza
authors.forename: M
authors.initials: M
authors.lastname: Chiu
authors.forename: A M
authors.initials: AM
authors.lastname: Hanby
authors.forename: R
authors.initials: R
authors.lastname: Poulsom
authors.forename: R B
authors.initials: RB
authors.lastname: Clarke
authors.forename: M
authors.initials: M
authors.lastname: Baron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D009857:Oncogenes / Q000235:genetics; D011379:Prognosis; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases