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BMC Cancer ; 19(1): 654, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269911

RESUMO

BACKGROUND: Yes-associated protein (YAP) plays a crucial role in tumour development and it is the main effector of the Hippo signalling pathway. However, the mechanism underlying YAP downregulation in laryngeal cancer is still unclear. In our previous study, we found that YAP, compared with adjacent tissues, was expressed higher in laryngeal cancer and was also closely associated with histological differentiation, TNM stage and poor prognosis. METHODS: In this study, we attempted to determine whether silenced YAP could downregulate human laryngeal carcinoma Hep-2 cells progression. YAP was downregulated in Hep-2 cells by shRNA, and the malignant ability of Hep-2 was assessed in vitro and in vivo. RESULTS: In vitro, CCK-8, colony formation and wound healing assays showed that downregulation of YAP significantly reduced the rates of proliferation, migration, and invasion in Hep-2 cells. Downregulation of YAP distinctly induced G2/M cycle arrest and increased the rate of apoptosis. Accordingly, western blot assay suggested that the expression of DKK1, vimentin and ß-catenin was significantly decreased after YAP downregulated treatment, thereby indicating that YAP mediated the EMT programme and the Wnt/ß-catenin signalling pathway in carcinoma of the larynx. Furthermore, silencing of YAP suppressed Hep-2 cell tumourigenesis and metastasis in vivo. CONCLUSION: In summary, our findings demonstrated the proliferation of YAP downregulation and the invasion of Hep-2 cells via downregulating the Wnt/ß-catenin pathway in vitro and in vivo, suggesting that YAP may provide a potential therapeutic strategy for the treatment of laryngeal cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patologia , Fosfoproteínas/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Movimento Celular , Proliferação de Células , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular , Técnicas de Silenciamento de Genes , Pontos de Checagem da Fase M do Ciclo Celular , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Estadiamento de Neoplasias , RNA Interferente Pequeno , Sincalida , Fatores de Transcrição , Ensaio Tumoral de Célula-Tronco , Vimentina/metabolismo , Via de Sinalização Wnt , Cicatrização , Proteínas de Sinalização YAP
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