23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Verteporfin inhibits YAP function through up-regulating 14-3-3σ sequestering YAP in the cytoplasm.

      Read this article at

      ScienceOpenPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Yes-associated protein (YAP), the central mediator of Hippo pathway, not only regulates a diversity of cellular processes during development but also plays a pivotal role in tumorigenesis. YAP is overexpressed in many types of human cancers with its expression level being associated with patient outcomes. Thus, inhibiting YAP function could provide a novel therapeutic approach. Verteporfin, a photosensitizer, which has been used in photodynamic therapy (PDT), was recently identified as an inhibitor of the interaction of YAP with TEAD, which, in turn, blocks transcriptional activation of targets downstream of YAP. However, the mechanism by which Verteporfin inhibits YAP activity remains to be elucidated. We demonstrate that overexpression of YAP stimulates cell proliferation whereas knocking down YAP or treating cells with Verteporfin inhibited cell proliferation, even in the presence of growth factors. Protoporphyrin IX, another photosensitizer, did not have similar activity demonstrating specificity to Verteporfin. Verteporfin induced sequestration of YAP in cytoplasm through increasing levels of 14-3-3σ, a YAP chaperon protein that retains YAP in cytoplasm and targets it for degradation in the proteosome. Interestingly, while knockdown of YAP had no effect on the ability of Verteporfin to induce 14-3-3σ, p53 is required for this effect of Verteporfin. This provides potential approaches to select patients likely to benefit from Verteporfin.

          Related collections

          Author and article information

          Journal
          Am J Cancer Res
          American journal of cancer research
          2156-6976
          2016
          : 6
          : 1
          Affiliations
          [1 ] Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan UniversityShanghai 200011, China; Department of Systems Biology, The University of Texas MD Anderson Cancer CenterHouston 77030, TX, USA.
          [2 ] Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital, Fudan University Shanghai 200011, China.
          [3 ] Department of Systems Biology, The University of Texas MD Anderson Cancer Center Houston 77030, TX, USA.
          Article
          4759394
          27073720
          1286ac6a-313a-4e29-a190-8aadbdcf9c20
          History

          14-3-3σ,Verteporfin,YAP,endometrial cancer
          14-3-3σ, Verteporfin, YAP, endometrial cancer

          Comments

          Comment on this article