TY - JOUR
T1 - Transcription Factors OVOL1 and OVOL2 Induce the Mesenchymal to Epithelial Transition in Human Cancer
AU - Roca, Hernan
AU - Hernandez, James
AU - Weidner, Savannah
AU - McEachin, Richard C.
AU - Fuller, David
AU - Sud, Sudha
AU - Schumann, Taibriana
AU - Wilkinson, John E.
AU - Zaslavsky, Alexander
AU - Li, Hangwen
AU - Maher, Christopher A.
AU - Daignault-Newton, Stephanie
AU - Healy, Patrick N.
AU - Pienta, Kenneth J.
PY - 2013/10/4
Y1 - 2013/10/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84885079783&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0076773
DO - 10.1371/journal.pone.0076773
M3 - Article
C2 - 24124593
AN - SCOPUS:84885079783
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 10
M1 - e76773
ER -