title: The Hippo transducer TAZ interacts with the SWI/SNF complex to regulate breast epithelial lineage commitment.
abstract: Lineage-committed cells of many tissues exhibit substantial plasticity in contexts such as wound healing and tumorigenesis, but the regulation of this process is not well understood. We identified the Hippo transducer WWTR1/TAZ in a screen of transcription factors that are able to prompt lineage switching of mammary epithelial cells. Forced expression of TAZ in luminal cells induces them to adopt basal characteristics, and depletion of TAZ in basal and/or myoepithelial cells leads to luminal differentiation. In human and mouse tissues, TAZ is active only in basal cells and is critical for basal cell maintenance during homeostasis. Accordingly, loss of TAZ affects mammary gland development, leading to an imbalance of luminal and basal populations as well as branching defects. Mechanistically, TAZ interacts with components of the SWI/SNF complex to modulate lineage-specific gene expression. Collectively, these findings uncover a new role for Hippo signaling in the determination of lineage identity through recruitment of chromatin-remodeling complexes.
authors.affiliation: Department of Developmental, Chemical, and Molecular Biology, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Skibinski
authors.affiliation: Department of Developmental, Chemical, and Molecular Biology, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA.
authors.forename: Jerrica L
authors.initials: JL
authors.lastname: Breindel
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology, Passeig de la Vall d'Hebron 119-129, Barcelona 08035, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Translational Genomics Group, Vall d'Hebron Institute of Oncology, Passeig de la Vall d'Hebron 119-129, Barcelona 08035, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Galván
authors.affiliation: Department of Developmental, Chemical, and Molecular Biology, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Smith
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Piyush B
authors.initials: PB
authors.lastname: Gupta
authors.affiliation: Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ 85287, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: LaBaer
authors.affiliation: Department of Developmental, Chemical, and Molecular Biology, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA; Molecular Oncology Research Institute, Tufts Medical Center, 800 Washington Street, Boston, MA 02111, USA. Electronic address: charlotte.kuperwasser@tufts.edu.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D000090683:Hippo Signaling Pathway; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000217:Acyltransferases; C486363:tafazzin protein, mouse; C108675:TAFAZZIN protein, human; D017346:Protein Serine-Threonine Kinases