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

Škalamera, Dubravka, Dahmer-Heath, Mareike, Stevenson, Alexander J., Pinto, Cletus, Shah, Esha T., Daignault, Sheena M., Said, Nur Akmarina B. M., Davis, Melissa, Haass, Nikolas K., Williams, Elizabeth D., Hollier, Brett G., Thompson, Erik W., Gabrielli, Brian, & Gonda, Thomas J. (2016) Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer. Oncotarget. (In Press)

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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.

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ID Code: 98729
Item Type: Journal Article
Refereed: Yes
Keywords: Breast cancer, Genome-wide gain-of-function screen, epithelial-to-mesenchymal transition
DOI: 10.18632/oncotarget.11314
ISSN: 1949-2553
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2016 Impact Journals, LLC
Copyright Statement: All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
Deposited On: 07 Sep 2016 22:18
Last Modified: 08 Sep 2016 23:34

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