YAP1 Regulates The Biological Behavior Of ESCC Cells By Targeting Hippo Pathway

Background: The incidence and mortality of esophageal cancer are high in China.The main pathological type of esophageal cancer is squamous cell carcinoma.Most patients with esophageal cancer are at an advanced stage when they are found.Some patients cannot tolerate the toxic side effects of immunotherapy,radiotherapy and Cisplatin(DDP)-based chemotherapy,resulting in poor treatment effect and poor prognosis.Therefore,a new and safe therapeutic target for esophageal cancer is particularly important.Through bioinformatics analysis,we found that Yes Protein 1(YAP1)was differentially expressed in esophageal squamous cell carcinoma,and the difference was statistically significant.It can enrich the Hippo pathway and multiple signaling pathways to play a biological role.YAP1 is a key transcriptional regulator in Hippo signaling pathway,which is closely related to the growth,metastasis,and drug resistance of various tumors.Verteporfin(VP)has been considered as a YAP1 inhibitor in recent years and is widely used in a variety of diseases,such as cancer and fibrosis.The aim of this study is to investigate the expression of YAP1 in esophageal squamous cell carcinoma(ESCC)cells TE1,TE12,and TE13 and its effect on the biological behavior of ESCC cells,to verify the inhibitory effect of VP on ESCC,to explore the potential mechanism of YAP1 in ESCC,and to provide theoretical basis for YAP1 as a new therapeutic target for ESCC.Methods: RT-qPCR and Western blot were used to detect the expression levels of YAP1 in three esophageal squamous cell carcinoma cell lines TE1,TE12,and TE13,and to observe the biological behaviors of esophageal squamous cell carcinoma cells with different YAP1 expression levels and their responses to chemotherapy drug Cisplatin(DDP).The YAP1 inhibitor VP was used to treat three ESCC cell lines TE1,TE12,and TE13,and the changes of YAP1 and its downstream target protein CTGF and the changes of cell biological behavior were observed to verify that YAP1 regulates the growth,migration,and invasion of ESCC cells through Hippo pathway.Results: By RT-qPCR and Western blot,we found that the expression levels of YAP1 in three ESCC cell lines TE1,TE12 and TE13 were higher than those in normal esophageal epithelial cells HEEC.TE1 cells had higher YAP1 expression level and stronger growth,migration,and invasion abilities than normal esophageal epithelial cells.However,TE12 and TE13 cells are more effective to DDP treatment.After treatment with VP,the expression levels of YAP1 and its downstream target protein CTGF were significantly decreased,and the biological behavior of esophageal squamous cell carcinoma cells was significantly inhibited.Conclusions: YAP1 is differentially expressed in the esophagus,and the increased expression of YAP1 can promote the malignant progression of ESCC cells.VP inhibits the growth,migration,and invasion of ESCC cells by inhibiting YAP1 and its downstream target protein CTGF.