Effect of YAP1 silencing on esophageal cancer.
BACKGROUND
YAP1, the nuclear effector of the Hippo pathway, has become an attractive target for treatment of malignancies and is a candidate oncogene in esophageal cancer (EC). We hypothesized that knockdown of YAP1 could suppress EC and could be used for targeted therapy. However, there are few reports of the effect of YAP1 knockdown in EC.


METHODS
Quantitative real-time polymerase chain reaction and Western blot assays were performed to determine the expression levels of YAP1 mRNA and protein in primary EC tissue samples, EC cell lines, and controls. Immunohistochemistry was also performed to detect YAP1 protein expression in primary EC tumor and matched nontumor control tissues. YAP1-knockdown cell lines were constructed using short-hairpin RNA, and MTT, flow cytometry, and transwell chamber assays were used to analyze the effect of YAP1 knockdown on EC cell proliferation, apoptosis, and invasion. In vivo tumor formation assays were used to investigate the antitumor effect of YAP1 knockdown.


RESULTS
We found that YAP1 mRNA and protein were upregulated in EC and that YAP1 expression correlated significantly with metastasis and tumor stage. We also found that YAP1 knockdown repressed cell proliferation and invasion and promoted apoptosis of EC cell lines. In addition, animal experiments revealed that YAP1 knockdown suppressed the growth of esophageal tumors in vivo.


CONCLUSIONS
Collectively, these data confirm our hypothesis that YAP1 knockdown suppresses EC and suggest that YAP1 knockdown could be exploited in the targeted gene therapy of EC in the future.
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Jia
J
Zhao
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Xiangnan
X
Li
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Yang
Y
Yang
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Dengyan
D
Zhu
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Chunyang
C
Zhang
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Donglei
D
Liu
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Kai
K
Wu
Department of Thoracic Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, People's Republic of China; Key Thoracic Tumour Experimental Laboratory of Zhengzhou, Zhengzhou, Henan, People's Republic of China.
Song
S
Zhao
Hippo; YAP1 knockdown; animal experiments; esophageal cancer