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

Jing Cai, Nailing Zhang, Yonggang Zheng, Roeland F. De Wilde, Anirban Maitra, Duojia Pan

Research output: Contribution to journalArticlepeer-review

298 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2383-2388
Number of pages6
JournalGenes and Development
Volume24
Issue number21
DOIs
StatePublished - Nov 1 2010

Keywords

  • Cancer
  • Growth control
  • Hippo signaling
  • Mouse
  • Regeneration

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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