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Updated: Jun 7, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Published on: September 13, 2018
The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
Jing Cai1, Nailing Zhang, Yonggang Zheng
1Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Abstract:
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.
Insights
Hippo signaling, involving Yes-associated protein (YAP), is crucial for intestinal regeneration. Its controlled activity balances compensatory proliferation and prevents polyp formation during tissue repair after injury.
Area of Science:
- Cell Biology
- Gastroenterology
- Developmental Biology
Background:
- The Hippo signaling pathway regulates organ size during development.
- Its role in adult tissue regeneration, particularly in the intestine, remains unclear.
Purpose of the Study:
- To investigate the function of Hippo signaling, specifically Yes-associated protein (YAP), in colonic tissue regeneration.
- To understand the implications of YAP activity in intestinal repair and polyp formation.
Main Methods:
- Utilized a dextran sodium sulfate (DSS)-induced mouse model for colonic regeneration.
- Analyzed Yes-associated protein (YAP) expression levels in regenerating intestinal crypts.
- Studied the effects of YAP inactivation and hyperactivation on DSS-induced intestinal regeneration and polyp formation.
Main Results:
- Regenerating colonic crypts showed increased Yes-associated protein (YAP) levels.
- YAP inactivation impaired DSS-induced intestinal regeneration but had no effect on normal intestinal homeostasis.
- YAP hyperactivation led to early-onset polyp formation following DSS treatment.
Conclusions:
- Yes-associated protein (YAP) is essential for effective colonic tissue regeneration.
- Precise control of YAP activity is critical during regeneration to promote compensatory proliferation while preventing oncogenic transformation.
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