Unraveling the expression of the oncogene YAP1, a Wnt/beta-catenin target, in adrenocortical tumors and its association with poor outcome in pediatric patients

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...

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Published in:	Oncotarget Vol. 7; no. 51; pp. 84634 - 84644
Main Authors:	Abduch, Rafael H, Carolina Bueno, Ana, Leal, Leticia F, Cavalcanti, Marcelo M, Gomes, Débora C, Brandalise, Silvia R, Masterallo, Maria J, Yunes, José A, Martinelli, Jr, Carlos E, Tone, Luiz G, Tucci, Silvio, Molina, Carlos A F, Ramalho, Fernando S, Moreira, Ayrton C, Cardinalli, Izilda A, Scrideli, Carlos A, Ramalho, Leandra N Z, de Castro, Margaret, Antonini, Sonir R
Format:	Journal Article
Language:	English
Published:	United States Impact Journals LLC 20-12-2016
Subjects:	Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Adolescent Adrenal Cortex - metabolism Adrenal Cortex Neoplasms - genetics Adrenal Cortex Neoplasms - metabolism Adrenal Cortex Neoplasms - mortality beta Catenin - metabolism Carcinogenesis Cell Line, Tumor Cell Proliferation Child Child, Preschool Female Gene Expression Regulation, Neoplastic Humans Infant Male Neoplasm Metastasis Neoplasm Recurrence, Local Phosphoproteins - genetics Phosphoproteins - metabolism Research Paper Signal Transduction Survival Analysis Transcription Factors Wnt Proteins - metabolism YAP-Signaling Proteins YAP1 Wnt/beta-catenin pathway adrenocortical tumor Hippo pathway outcome
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Summary:	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. 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. 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. 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. 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.
ISSN:	1949-2553 1949-2553
DOI:	10.18632/oncotarget.12382