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

Adam Skibinski1, Jerrica L Breindel1, Aleix Prat2

  • 1Department 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.

Cell Reports
|March 12, 2014
PubMed
Summary

The Hippo pathway’s WWTR1/TAZ protein controls mammary cell identity. TAZ (WWTR1) regulates mammary gland development and lineage determination by interacting with chromatin remodelers.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Signaling Pathways

Background:

  • Lineage-committed cells show plasticity during wound healing and cancer.
  • Regulation of cell plasticity is not fully understood.

Purpose of the Study:

  • Identify transcription factors regulating mammary epithelial cell lineage switching.
  • Investigate the role of Hippo pathway transducer WWTR1/TAZ in mammary gland development and cell identity.

Main Methods:

  • Screened transcription factors for lineage switching ability.
  • Utilized forced expression and depletion of TAZ in mammary epithelial cells.
  • Examined TAZ activity in human and mouse mammary tissues.
  • Investigated TAZ interaction with the SWI/SNF complex.

Main Results:

  • WWTR1/TAZ was identified as a key regulator of mammary epithelial cell lineage.
  • Forced TAZ expression in luminal cells induced basal characteristics; TAZ depletion in basal cells caused luminal differentiation.
  • TAZ is active in basal cells and essential for their maintenance during homeostasis.
  • Loss of TAZ impaired mammary gland development, causing population imbalance and branching defects.
  • TAZ interacts with the SWI/SNF complex to modulate lineage-specific gene expression.

Conclusions:

  • WWTR1/TAZ plays a critical role in determining mammary cell lineage identity.
  • Hippo signaling, via TAZ, regulates cell fate through chromatin remodeling.
  • Findings reveal a novel mechanism for lineage determination in the mammary gland.