title: Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer.
abstract: Epithelial to mesenchymal transition (EMT) is a developmental program that has been implicated in progression, metastasis and therapeutic resistance of some carcinomas. To identify genes whose overexpression drives EMT, we screened a lentiviral expression library of 17000 human open reading frames (ORFs) using high-content imaging to quantitate cytoplasmic vimentin. Hits capable of increasing vimentin in the mammary carcinoma-derived cell line MDA-MB-468 were confirmed in the non-tumorigenic breast-epithelial cell line MCF10A. When overexpressed in this model, they increased the rate of cell invasion through Matrigel™, induced mesenchymal marker expression and reduced expression of the epithelial marker E-cadherin. In gene-expression datasets derived from breast cancer patients, the expression of several novel genes correlated with expression of known EMT marker genes, indicating their in vivo relevance. As EMT-associated properties are thought to contribute in several ways to cancer progression, genes identified in this study may represent novel targets for anti-cancer therapy.
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.|Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Škalamera
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.|Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
authors.forename: Mareike
authors.initials: M
authors.lastname: Dahmer-Heath
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.|Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevenson
authors.affiliation: St Vincent's Institute of Medical Research and University of Melbourne Department of Surgery, St. Vincent's Hospital, Melbourne, VIC, Australia.
authors.forename: Cletus
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Brisbane, QLD, Australia.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology,Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Esha T
authors.initials: ET
authors.lastname: Shah
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Sheena M
authors.initials: SM
authors.lastname: Daignault
authors.affiliation: Monash Institute of Medical Research (now Hudson Institute of Medical Research), Monash University, Melbourne, VIC, Australia.|University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nur Akmarina B M
authors.initials: NA
authors.lastname: Said
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
authors.forename: Melissa
authors.initials: M
authors.lastname: Davis
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Nikolas K
authors.initials: NK
authors.lastname: Haass
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Brisbane, QLD, Australia.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology,Translational Research Institute, Brisbane, QLD, Australia.|Monash Institute of Medical Research (now Hudson Institute of Medical Research), Monash University, Melbourne, VIC, Australia.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Williams
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, Brisbane, QLD, Australia.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology,Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Brett G
authors.initials: BG
authors.lastname: Hollier
authors.affiliation: St Vincent's Institute of Medical Research and University of Melbourne Department of Surgery, St. Vincent's Hospital, Melbourne, VIC, Australia.|Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology,Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Erik W
authors.initials: EW
authors.lastname: Thompson
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.|Mater Medical Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Gabrielli
authors.affiliation: University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.|School of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gonda
mesh_terms: D015703:Antigens, CD; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D014746:Vimentin
keywords: breast cancer; epithelial-mesenchymal transition; high-content-screening; lentiviral vectors; vimentin