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Genes Dev. 2012 Jun 15;26(12):1300-5. doi: 10.1101/gad.192856.112. Epub 2012 Jun 7.

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

Author information

1
Howard Hughes Medical Institute, Maryland, USA.

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.

PMID:
22677547
PMCID:
PMC3387657
DOI:
10.1101/gad.192856.112
[Indexed for MEDLINE]
Free PMC Article

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