title: Mammary morphogenesis and regeneration require the inhibition of EMT at terminal end buds by Ovol2 transcriptional repressor.
abstract: Epithelial cells possess remarkable plasticity, having the ability to become mesenchymal cells through alterations in adhesion and motility (epithelial-to-mesenchymal transition [EMT]). However, how epithelial plasticity is kept in check in epithelial cells during tissue development and regeneration remains to be fully understood. Here we show that restricting the EMT of mammary epithelial cells by transcription factor Ovol2 is required for proper morphogenesis and regeneration. Deletion of Ovol2 blocks mammary ductal morphogenesis, depletes stem and progenitor cell reservoirs, and leads epithelial cells to undergo EMT in vivo to become nonepithelial cell types. Ovol2 directly represses myriad EMT inducers, and its absence switches response to TGF-β from growth arrest to EMT. Furthermore, forced expression of the repressor isoform of Ovol2 is able to reprogram metastatic breast cancer cells from a mesenchymal to an epithelial state. Our findings underscore the critical importance of exquisitely regulating epithelial plasticity in development and cancer.
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Villarreal-Ponce
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Salmans
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Magid
authors.initials: M
authors.lastname: Fallahi
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA; Department of Medicine, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: xdai@uci.edu.
authors.forename: Xing
authors.initials: X
authors.lastname: Dai
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming; D004627:Embryonic Induction; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D012038:Regeneration; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C491431:MOVO protein, mouse; D014157:Transcription Factors; D016212:Transforming Growth Factor beta
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