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PLoS One. 2013 Oct 4;8(10):e76773. doi: 10.1371/journal.pone.0076773. eCollection 2013.

Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer.

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1
Department of Urology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.

Abstract

Cell plasticity regulated by the balance between the mesenchymal to epithelial transition (MET) and the opposite program, EMT, is critical in the metastatic cascade. Several transcription factors (TFs) are known to regulate EMT, though the mechanisms of MET remain unclear. We demonstrate a novel function of two TFs, OVOL1 and OVOL2, as critical inducers of MET in human cancers. Our findings indicate that the OVOL-TFs control MET through a regulatory feedback loop with EMT-inducing TF ZEB1, and the regulation of mRNA splicing by inducing Epithelial Splicing Regulatory Protein 1 (ESRP1). Using mouse prostate tumor models we show that expression of OVOL-TFs in mesenchymal prostate cancer cells attenuates their metastatic potential. The role of OVOL-TFs as inducers of MET is further supported by expression analyses in 917 cancer cell lines, suggesting their role as crucial regulators of epithelial-mesenchymal cell plasticity in cancer.

PMID:
24124593
PMCID:
PMC3790720
DOI:
10.1371/journal.pone.0076773
[Indexed for MEDLINE]
Free PMC Article
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