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10.18632/oncotarget.12382

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suck abstract from ncbi


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pmid27705928
      Oncotarget 2016 ; 7 (51 ): 84634-84644
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  • Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in adrenocortical tumors and its association with poor outcome in pediatric patients #MMPMID27705928
  • Abduch RH ; Carolina Bueno A ; Leal LF ; Cavalcanti MM ; Gomes DC ; Brandalise SR ; Masterallo MJ ; Yunes JA ; Martinelli CE Jr ; Tone LG ; Tucci S ; Molina CA ; Ramalho FS ; Moreira AC ; Cardinalli IA ; Scrideli CA ; Ramalho LN ; de Castro M ; Antonini SR
  • Oncotarget 2016[Dec]; 7 (51 ): 84634-84644 PMID27705928 show ga
  • BACKGROUND: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is associated with increased cell proliferation in human cancers. YAP1 is a potential target of the Wnt/beta-catenin pathway, which plays an important role in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis has not been assessed. AIMS: To evaluate YAP1 expression in normal adrenals and pediatric ACT and its association with disease outcome. To investigate the interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical cells. RESULTS: Strong YAP1 staining was present in fetal adrenals and pediatric ACT but weak in postnatal adrenals. In pediatric ACT, YAP1 mRNA overexpression was associated with death, recurrent/metastatic disease and lower overall survival. The inhibition of the Wnt/beta-catenin pathway increased YAP1 mRNA expression. siYAP1 increased CTNNB1/beta-catenin expression and nuclear staining regardless of DLV2, moreover, it decreased cell growth and impaired cell migration. MATERIALS AND METHODS: We assessed in 42 pediatric ACT samples the YAP1 protein expression by immunohistochemistry and mRNA expression by RT-qPCR and analyzed their association with outcome. As controls, we resort 32 fetal and postnatal normal adrenals for IHC and 10 normal adrenal cortices for RT-qPCR. The interaction between YAP1 and the Wnt/beta-catenin pathway was assessed in NCI-H295 adrenocortical cells by inhibiting the TCF/beta-catenin complex and by knocking down YAP1. CONCLUSION: YAP1 overexpression is a marker of poor prognosis for pediatric patients with ACT. In adrenocortical cells, there is a close crosstalk between YAP1 and Wnt/beta-catenin. These data open the possibility of future molecular therapies targeting Hippo/YAP1 signaling to treat advanced ACT.
  • |Adaptor Proteins, Signal Transducing/genetics/*metabolism [MESH]
  • |Adolescent [MESH]
  • |Adrenal Cortex Neoplasms/genetics/*metabolism/mortality [MESH]
  • |Adrenal Cortex/*metabolism [MESH]
  • |Carcinogenesis [MESH]
  • |Cell Line, Tumor [MESH]
  • |Cell Proliferation [MESH]
  • |Child [MESH]
  • |Child, Preschool [MESH]
  • |Female [MESH]
  • |Gene Expression Regulation, Neoplastic [MESH]
  • |Humans [MESH]
  • |Infant [MESH]
  • |Male [MESH]
  • |Neoplasm Metastasis [MESH]
  • |Neoplasm Recurrence, Local [MESH]
  • |Phosphoproteins/genetics/*metabolism [MESH]
  • |Signal Transduction [MESH]
  • |Survival Analysis [MESH]
  • |Transcription Factors [MESH]
  • |Wnt Proteins/metabolism [MESH]
  • |YAP-Signaling Proteins [MESH]


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