β-catenin destruction complex-independent regulation of Hippo-YAP signaling by APC in intestinal tumorigenesis

Jing Cai, Anirban Maitra, Robert A. Anders, Makoto M. Taketo, Duojia Pan

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Mutations in Adenomatous polyposis coli (APC) underlie familial adenomatous polyposis (FAP), an inherited cancer syndrome characterized by the widespread development of colorectal polyps. APC is best known as a scaffold protein in the β-catenin destruction complex, whose activity is antagonized by canonical Wnt signaling. Whether other effector pathways mediate APC’s tumor suppressor function is less clear. Here we report that activation of YAP, the downstream effector of the Hippo signaling pathway, is a general hallmark of tubular adenomas from FAP patients. We show that APC functions as a scaffold protein that facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1. Consistent with the molecular link between APC and the Hippo signaling pathway, genetic analysis reveals that YAP is absolutely required for the development of APC-deficient adenomas. These findings establish Hippo-YAP signaling as a critical effector pathway downstream from APC, independent from its involvement in the β-catenin destruction complex.

Original languageEnglish (US)
Pages (from-to)1493-1506
Number of pages14
JournalGenes and Development
Volume29
Issue number14
DOIs
StatePublished - Jan 1 2015

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Catenins
Adenomatous Polyposis Coli
Carcinogenesis
Adenoma
Critical Pathways
Polyps
Neoplasms
Phosphotransferases
Mutation

Keywords

  • APC
  • Hippo signaling
  • TAZ
  • Tumorigenesis
  • YAP
  • β-catenin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

β-catenin destruction complex-independent regulation of Hippo-YAP signaling by APC in intestinal tumorigenesis. / Cai, Jing; Maitra, Anirban; Anders, Robert A.; Taketo, Makoto M.; Pan, Duojia.

In: Genes and Development, Vol. 29, No. 14, 01.01.2015, p. 1493-1506.

Research output: Contribution to journalArticle

Cai, Jing ; Maitra, Anirban ; Anders, Robert A. ; Taketo, Makoto M. ; Pan, Duojia. / β-catenin destruction complex-independent regulation of Hippo-YAP signaling by APC in intestinal tumorigenesis. In: Genes and Development. 2015 ; Vol. 29, No. 14. pp. 1493-1506.
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