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Multiple roles for the hippo effector yap in gut regeneration and cancer initiation

Alex Gregorieff1, Jeffrey L Wrana2

  • 1Centre for Systems Biology, and Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada.

Molecular & Cellular Oncology
|June 18, 2016
PubMed

Insights

Yes-associated protein (Yap) drives intestinal regeneration by reprogramming stem cells and blocking differentiation. Yap also promotes tumor growth by working with Wnt signaling in cancer stem cells.

Area of Science:

  • Cell biology
  • Developmental biology
  • Cancer biology

Background:

  • The Hippo signaling pathway regulates organ size and tissue homeostasis.
  • Yes-associated protein (Yap) is a key downstream effector of the Hippo pathway.
  • Yap's role in adult stem cell function and cancer is an area of active investigation.

Purpose of the Study:

  • To investigate the role of Yap in intestinal regeneration.
  • To determine how Yap influences intestinal stem cell behavior.
  • To explore the interplay between Yap and Wnt signaling in intestinal tumorigenesis.

Main Methods:

  • Utilized mouse models of intestinal injury and regeneration.
  • Employed genetic manipulation to control Yap activity in intestinal stem cells.
  • Analyzed gene expression and cell differentiation markers.
  • Investigated the effects of Yap activation in combination with Wnt signaling in preclinical cancer models.

Main Results:

  • Yap promotes intestinal regeneration by preventing terminal differentiation of intestinal stem cells.
  • Yap reprogramming of stem cells is crucial for effective tissue repair.
  • Yap signaling cooperates with Wnt activation to drive the formation of intestinal adenomas.
  • Yap's function in tumor-initiating cells highlights its role in cancer stem cell biology.

Conclusions:

  • Yap is a critical regulator of intestinal regeneration through stem cell reprogramming.
  • Yap's pro-regenerative function has implications for understanding tissue repair mechanisms.
  • Yap and Wnt signaling form a synergistic axis driving intestinal tumor initiation and growth.
  • Targeting Yap may offer therapeutic strategies for intestinal diseases and cancers.
Keywords:
EgfrPaneth cellsWntYaphippointestinal stem cells

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