title: Transcription factors OVOL1 and OVOL2 induce the mesenchymal to epithelial transition in human cancer.
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.
authors.affiliation: Department of Urology, University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Hernan
authors.initials: H
authors.lastname: Roca
authors.forename: James
authors.initials: J
authors.lastname: Hernandez
authors.forename: Savannah
authors.initials: S
authors.lastname: Weidner
authors.forename: Richard C
authors.initials: RC
authors.lastname: McEachin
authors.forename: David
authors.initials: D
authors.lastname: Fuller
authors.forename: Sudha
authors.initials: S
authors.lastname: Sud
authors.forename: Taibriana
authors.initials: T
authors.lastname: Schumann
authors.forename: John E
authors.initials: JE
authors.lastname: Wilkinson
authors.forename: Alexander
authors.initials: A
authors.lastname: Zaslavsky
authors.forename: Hangwen
authors.initials: H
authors.lastname: Li
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Maher
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault-Newton
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Healy
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D064593:Heterografts; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012326:RNA Splicing; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; C490319:OVOL1 protein, human; C544941:Ovol2 protein, human; D014157:Transcription Factors