Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer

Hernan Roca, James Hernandez, Savannah Weidner, Richard C. McEachin, David Fuller, Sudha Sud, Taibriana Schumann, John E. Wilkinson, Alexander Zaslavsky, Hangwen Li, Christopher A. Maher, Stephanie Daignault-Newton, Patrick N. Healy, Kenneth Pienta

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere76773
JournalPLoS One
Volume8
Issue number10
DOIs
StatePublished - Oct 4 2013
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Transcription Factors
transcription factors
neoplasms
Neoplasms
prostatic neoplasms
Plasticity
Cells
Protein Splicing
regulatory proteins
Tumors
Prostate
Prostatic Neoplasms
epithelial cells
Epithelial Cells
cell lines
Feedback
Cell Line
Messenger RNA
mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer. / Roca, Hernan; Hernandez, James; Weidner, Savannah; McEachin, Richard C.; Fuller, David; Sud, Sudha; Schumann, Taibriana; Wilkinson, John E.; Zaslavsky, Alexander; Li, Hangwen; Maher, Christopher A.; Daignault-Newton, Stephanie; Healy, Patrick N.; Pienta, Kenneth.

In: PLoS One, Vol. 8, No. 10, e76773, 04.10.2013.

Research output: Contribution to journalArticle

Roca, H, Hernandez, J, Weidner, S, McEachin, RC, Fuller, D, Sud, S, Schumann, T, Wilkinson, JE, Zaslavsky, A, Li, H, Maher, CA, Daignault-Newton, S, Healy, PN & Pienta, K 2013, 'Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer', PLoS One, vol. 8, no. 10, e76773. https://doi.org/10.1371/journal.pone.0076773
Roca, Hernan ; Hernandez, James ; Weidner, Savannah ; McEachin, Richard C. ; Fuller, David ; Sud, Sudha ; Schumann, Taibriana ; Wilkinson, John E. ; Zaslavsky, Alexander ; Li, Hangwen ; Maher, Christopher A. ; Daignault-Newton, Stephanie ; Healy, Patrick N. ; Pienta, Kenneth. / Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer. In: PLoS One. 2013 ; Vol. 8, No. 10.
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