Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2014 Mar 27;6(6):1059-72. doi: 10.1016/j.celrep.2014.02.038. Epub 2014 Mar 6.

The Hippo transducer TAZ interacts with the SWI/SNF complex to regulate breast epithelial lineage commitment.

Author information

1
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.
2
Translational Genomics Group, Vall d'Hebron Institute of Oncology, Passeig de la Vall d'Hebron 119-129, Barcelona 08035, Spain.
3
Department of Developmental, Chemical, and Molecular Biology, Tufts University, 145 Harrison Avenue, Boston, MA 02111, USA.
4
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
6
Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 727 East Tyler Street, Tempe, AZ 85287, USA.
7
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.

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.

PMID:
24613358
PMCID:
PMC4011189
DOI:
10.1016/j.celrep.2014.02.038
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center