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Genes & Dev. 24 (21): 2383-2388

Copyright © 2010 by Cold Spring Harbor Laboratory Press.


RESEARCH COMMUNICATION

The Hippo signaling pathway restricts the oncogenic potential of an intestinal regeneration program

Jing Cai1, Nailing Zhang1, Yonggang Zheng1, Roeland F. de Wilde2, Anirban Maitra2,, and Duojia Pan1,3

1 Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;
2 Department 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.

Key Words: Hippo signaling • cancer • growth control • mouse • regeneration

Received for publication August 5, 2010. Accepted for publication September 14, 2010.


3 Corresponding author.

E-MAIL djpan{at}jhmi.edu; FAX (410) 502-3177.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1978810.

Supplemental material is available at http://www.genesdev.org.


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