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The Hippo Pathway in Intestinal Regeneration, Fetal Reprogramming, and Tumorigenesis.

Vanessa Man1,2, Jeffrey L Wrana3,2

  • 1Centre for Systems Biology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

Cold Spring Harbor Perspectives in Biology
|May 18, 2026
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Summary
This summary is machine-generated.

The Hippo pathway regulates organ size and intestinal regeneration. Its core components, YAP/TAZ, promote stem cell revival and tissue repair after injury, but their dysregulation links to colorectal cancer.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Biology

Background:

  • The Hippo signaling pathway is a conserved regulator of organ size and tissue homeostasis.
  • In mammals, core kinases MST1/2 and LATS1/2 regulate transcriptional coactivators YAP and TAZ.
  • YAP/TAZ activity is normally repressed in the intestine but promotes regeneration after injury.

Purpose of the Study:

  • To elucidate the role of the Hippo signaling pathway in intestinal regeneration.
  • To understand the mechanisms by which YAP/TAZ signaling drives repair and stem cell emergence.
  • To explore the connection between Hippo pathway dysregulation and colorectal cancer.

Main Methods:

  • Investigated Hippo pathway components and their targets (YAP/TAZ) in intestinal injury models.
  • Analyzed gene expression changes, including fetal gene re-expression and Clusterin (Clu) expression.
  • Examined the emergence of revival stem cells (revSCs) and their role in restoring Lgr5+ stem cells.

Main Results:

  • Transient YAP/TAZ activation following intestinal injury initiates a regenerative program.
  • This program involves fetal gene re-expression and the generation of Clu-positive revSCs.
  • These revSCs are crucial for restoring Lgr5+ intestinal stem cells and epithelial integrity.

Conclusions:

  • The Hippo pathway, particularly YAP/TAZ signaling, is essential for intestinal regeneration.
  • Cross-talk with WNT, TGF-β, and p53 signaling orchestrates this repair process.
  • Dysregulation of Hippo pathway interactions contributes to colorectal cancer development.