Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer.

Autor:	Škalamera D; 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., Dahmer-Heath M; 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., Stevenson AJ; 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., Pinto C; St Vincent's Institute of Medical Research and University of Melbourne Department of Surgery, St. Vincent's Hospital, Melbourne, VIC, Australia., Shah ET; 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., Daignault SM; University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia., Said NA; Monash Institute of Medical Research (now Hudson Institute of Medical Research), Monash University, Melbourne, VIC, Australia.; University of Malaya, Kuala Lumpur, Malaysia., Davis M; The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia., Haass NK; University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia., Williams ED; 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., Hollier BG; 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., Thompson EW; 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., Gabrielli B; 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., Gonda TJ; University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Brisbane, QLD, Australia.; School of Pharmacy, University of Queensland, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2016 Sep 20; Vol. 7 (38), pp. 61000-61020.
DOI:	10.18632/oncotarget.11314
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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