Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer
AuthorSkalamera, D; Dahmer-Heath, M; Stevenson, AJ; Pinto, C; Shah, ET; Daignault, SM; Said, NABM; Davis, M; Haass, NK; Williams, ED; ...
PublisherIMPACT JOURNALS LLC
AffiliationSurgery (St Vincent's)
Document TypeJournal Article
CitationsSkalamera, D., Dahmer-Heath, M., Stevenson, A. J., Pinto, C., Shah, E. T., Daignault, S. M., Said, N. A. B. M., Davis, M., Haass, N. K., Williams, E. D., Hollier, B. G., Thompson, E. W., Gabrielli, B. & Gonda, T. J. (2016). Genome-wide gain-of-function screen for genes that induce epithelial-to-mesenchymal transition in breast cancer. ONCOTARGET, 7 (38), pp.61000-61020. https://doi.org/10.18632/oncotarget.11314.
Access StatusOpen Access
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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