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10.18632/oncotarget.12382

http://scihub22266oqcxt.onion/10.18632/oncotarget.12382
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C5356687!5356687!27705928
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suck abstract from ncbi


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pmid27705928      Oncotarget 2016 ; 7 (51): 84634-44
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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; Bueno AC; Leal LF; Cavalcanti MM; Gomes DC; Brandalise SR; Masterallo MJ; Yunes JA; Martinelli CE; 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): 84634-44 PMID27705928show 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.
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