Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP

Yi Liu-Chittenden, Bo Huang, Joong Sup Shim, Qian Chen, Se Jin Lee, Robert A Anders, Jun Liu, Duojia Pan

Research output: Contribution to journalArticle

Abstract

The Drosophila TEAD ortholog Scalloped is required for Yki-mediated overgrowth but is largely dispensable for normal tissue growth, suggesting that its mammalian counterpart may be exploited for selective inhibition of oncogenic growth driven by YAP hyperactivation. Here we test this hypothesis genetically and pharmacologically. We show that a dominant-negative TEAD molecule does not perturb normal liver growth but potently suppresses hepatomegaly/tumorigenesis resulting from YAP overexpression or Neurofibromin 2 (NF2)/Merlin inactivation. We further identify verteporfin as a small molecule that inhibits TEAD-YAP association and YAP-induced liver overgrowth. These findings provide proof of principle that inhibiting TEAD-YAP interactions is a pharmacologically viable strategy against the YAP oncoprotein.

Original languageEnglish (US)
Pages (from-to)1300-1305
Number of pages6
JournalGenes & development
Volume26
Issue number12
DOIs
StatePublished - Jun 2012

Fingerprint

Neurofibromin 2
Pharmacology
Growth
Hepatomegaly
Liver
Oncogene Proteins
Drosophila
Carcinogenesis

Keywords

  • Chemical biology
  • Hippo signaling
  • Oncogene
  • YAP

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. / Liu-Chittenden, Yi; Huang, Bo; Shim, Joong Sup; Chen, Qian; Lee, Se Jin; Anders, Robert A; Liu, Jun; Pan, Duojia.

In: Genes & development, Vol. 26, No. 12, 06.2012, p. 1300-1305.

Research output: Contribution to journalArticle

Liu-Chittenden, Yi ; Huang, Bo ; Shim, Joong Sup ; Chen, Qian ; Lee, Se Jin ; Anders, Robert A ; Liu, Jun ; Pan, Duojia. / Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. In: Genes & development. 2012 ; Vol. 26, No. 12. pp. 1300-1305.
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