The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program
- 1Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
- 2Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, 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.
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Footnotes
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↵3 Corresponding author.
E-MAIL djpan{at}jhmi.edu; FAX (410) 502-3177.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1978810.
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Supplemental material is available at http://www.genesdev.org.
- Received August 5, 2010.
- Accepted September 14, 2010.
- Copyright © 2010 by Cold Spring Harbor Laboratory Press