Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway

Abstract 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...

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Main Authors: Xiaomin Tang, Yuxuan Sun, Ganglun Wan, Jiaqiang Sun, Jingwu Sun, Chunchen Pan
Format: Article
Language:English
Published: BMC 2019-07-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-019-5832-9
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author Xiaomin Tang
Yuxuan Sun
Ganglun Wan
Jiaqiang Sun
Jingwu Sun
Chunchen Pan
author_facet Xiaomin Tang
Yuxuan Sun
Ganglun Wan
Jiaqiang Sun
Jingwu Sun
Chunchen Pan
author_sort Xiaomin Tang
collection DOAJ
description Abstract 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 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. Conclusion In 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.
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spelling doaj.art-7a2b76176d5d40d4a19ba5cf097c4e642022-12-22T01:58:27ZengBMCBMC Cancer1471-24072019-07-0119111210.1186/s12885-019-5832-9Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathwayXiaomin Tang0Yuxuan Sun1Ganglun Wan2Jiaqiang Sun3Jingwu Sun4Chunchen Pan5Department of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityDepartment of Otolaryngology-Head and Neck Surgery, The Provincial Hospital affiliated to Anhui Medical UniversityAbstract 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 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. Conclusion In 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.http://link.springer.com/article/10.1186/s12885-019-5832-9YAPlaryngeal cancerWnt/β-cateninHep-2EMT
spellingShingle Xiaomin Tang
Yuxuan Sun
Ganglun Wan
Jiaqiang Sun
Jingwu Sun
Chunchen Pan
Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
BMC Cancer
YAP
laryngeal cancer
Wnt/β-catenin
Hep-2
EMT
title Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
title_full Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
title_fullStr Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
title_full_unstemmed Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
title_short Knockdown of YAP inhibits growth in Hep-2 laryngeal cancer cells via epithelial-mesenchymal transition and the Wnt/β-catenin pathway
title_sort knockdown of yap inhibits growth in hep 2 laryngeal cancer cells via epithelial mesenchymal transition and the wnt β catenin pathway
topic YAP
laryngeal cancer
Wnt/β-catenin
Hep-2
EMT
url http://link.springer.com/article/10.1186/s12885-019-5832-9
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