Abstract
BackgroundYes-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.MethodsIn 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.ResultsIn 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 β-catenin was significantly decreased after YAP downregulated treatment, thereby indicating that YAP mediated the EMT programme and the Wnt/β-catenin signalling pathway in carcinoma of the larynx. Furthermore, silencing of YAP suppressed Hep-2 cell tumourigenesis and metastasis in vivo.ConclusionIn summary, our findings demonstrated the proliferation of YAP downregulation and the invasion of Hep-2 cells via downregulating the Wnt/β-catenin pathway in vitro and in vivo, suggesting that YAP may provide a potential therapeutic strategy for the treatment of laryngeal cancer.
Highlights
Yes-associated protein (YAP) plays a crucial role in tumour development and it is the main effector of the Hippo signalling pathway
Untransfected isotype Hep-2 cells (Control group) and negative control Short hairpin ribonucleic acid (shRNA) (YAPNC shRNA) transfected Hep-2 cells were used as controls
These results indicated that downregulated YAP might inhibit growth in Hep-2 cells
Summary
Yes-associated protein (YAP) plays a crucial role in tumour development and it is the main effector of the Hippo signalling pathway. We found that YAP, compared with adjacent tissues, was expressed higher in laryngeal cancer and was closely associated with histological differentiation, TNM stage and poor prognosis. Yes-associated protein (YAP), a promoter of ligand binding, can regulate signal transduction and gene transcription in cells. It plays a vital role in regulating tissue regeneration and cancer development [4]. Previous studies demonstrated that YAP was highly expressed in most human cancer tissues such as liver cancer [5].
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