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Intestinal regeneration: YAP-tumor suppressor and oncoprotein?

Vivian S W Li1, Hans Clevers

  • 1Hubrecht Institute - KNAW and University Medical Centre Utrecht, Uppsalalaan 8, 3584CT Utrecht, The Netherlands. vli@nimr.mrc.ac.uk

Current Biology : CB
|February 9, 2013
PubMed

Insights

The Hippo pathway normally suppresses growth. Paradoxically, removing YAP, a key part of this pathway, surprisingly boosted intestinal stem cell regeneration.

Area of Science:

  • Cell biology
  • Molecular biology
  • Developmental biology

Background:

  • The Hippo signaling pathway regulates organ size by controlling cell proliferation and apoptosis.
  • Yki/YAP (Yes-associated protein) is a transcription co-activator targeted by the Hippo pathway.
  • YAP typically acts as an oncogene, promoting cell growth.

Purpose of the Study:

  • To investigate the role of YAP in intestinal stem cell function.
  • To reconcile the known growth-suppressive function of Hippo signaling with observations of YAP's role in regeneration.

Main Methods:

  • Genetic manipulation to remove YAP in intestinal stem cells.
  • Analysis of stem cell proliferation and tissue regeneration in vivo.
  • Assessment of downstream signaling pathways.

Main Results:

  • Genetic ablation of YAP led to enhanced intestinal stem cell expansion.
  • YAP removal promoted significant regeneration of the intestinal epithelium.
  • This contrasts with YAP's generally accepted role in promoting proliferation.

Conclusions:

  • YAP plays a complex, context-dependent role in intestinal homeostasis.
  • The Hippo pathway's regulation of stem cells is more nuanced than previously understood.
  • Targeting YAP may offer therapeutic potential for intestinal regeneration.

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