| Texto completo | |
| Autor(es): Mostrar menos - |
More, Candy C. B.
;
Bueno, Ana Carolina
;
Rojas, Cesar A. O.
;
Stecchini, Monica F.
;
Ramalho, Fernando S.
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Brandalise, Silvia R.
;
Cardinalli, Izilda A.
;
Yunes, Jose Andres
;
Junqueira, Thais
;
Scrideli, Carlos A.
;
Castro, Margaret
;
Antonini, Sonir R. R.
Número total de Autores: 12
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| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. N/A, p. 13-pg., 2025-01-27. |
| Resumo | |
Context Adrenocortical cancer (ACC) is rare and aggressive, with YAP1 overexpression associated with poor outcomes in pediatric patients.Objective In this study, we investigated the mechanisms by which YAP1 drives ACC progression and explored it as a potential target therapy.Methods YAP1 expression and methylation in ACC were analyzed from pediatric and adult cohorts. The role of YAP1 on ACC progression was examined in vitro using an adrenocortical cell line. Also, was evaluated the YAP1's influence on beta-catenin. The effect of YAP1 pharmacological inhibition was assessed on tumor growth in a murine xenograft model of ACC.Results High YAP1 expression was associated with lower survival in all cohorts. The YAP1 methylation signature was associated with patients' prognosis. Inhibition of YAP1 reduced ACC cell viability through cell cycle arrest in the G0/G1 phase, and inhibited the epithelial-mesenchymal transition and cell invasion. YAP1 modulated beta-catenin protein levels and transcription activity, whereas beta-catenin partially mediated the effect of YAP1 on adrenocortical tumorigenesis. In vivo, verteporfin impaired tumor growth and Ki67 immunoreactivity in xenografts.Conclusion YAP1 is a potential novel prognostic marker in patients with ACC. Its deregulation contributes to adrenocortical tumorigenesis partially through crosstalk between Hippo/YAP1 and Wnt/beta-catenin pathways. YAP1 inhibition is a new antitumor target. (AU) | |
| Processo FAPESP: | 19/00860-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-generation sequencing). |
| Beneficiário: | Ana Carolina Bueno de Queiroz Arruda |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/03989-6 - Mecanismos fisiopatológicos e moleculares de tumorigênese: abordagem baseada em plataformas de sequenciamento em escala genômica (NGS - Next-Generation Sequencing) |
| Beneficiário: | Margaret de Castro |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 15/19663-5 - Investigação das bases moleculares da tumorigênese adrenocortical e busca por novos alvos terapêuticos |
| Beneficiário: | Sonir Roberto Rauber Antonini |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/17737-7 - Papel do oncogene YAP1 no processo de tumorigênese e metástase e efeito de seu inibidor verteporfina nos tumores adrenocorticais pediátricos |
| Beneficiário: | Candy Christie Bellido More |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado Direto |