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

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          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.

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          Author and article information

          Journal
          Genes Dev
          Genes & development
          Cold Spring Harbor Laboratory
          1549-5477
          0890-9369
          Jun 15 2012
          : 26
          : 12
          Affiliations
          [1 ] Howard Hughes Medical Institute, Maryland, USA.
          Article
          gad.192856.112
          10.1101/gad.192856.112
          3387657
          22677547
          6d997914-144a-438c-bfe4-ca1712e89126
          History

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