Nectin-4 Promotes The Invasion And Metastasis Of Gastric Cancer Through Epithelial-Mesenchymal Transformation

Objective:To detect the clinical significances and the expressions of nectin-4 and epithelial-mesenchymal transition(EMT)related proteins in human gastric cancer,and to explore the role of nectin-4-mediated EMT in the invasion and metastasis of gastric cancer.Method:The expressions of nectin-4 mRNA and protein were detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blot in 120 gastric cancer cases.The expressions of nectin-4 and EMT-related proteins in 120 gastric cancer tissues and adjacent normal gastric mucosas were examined through immunohistochemistry.Afterwards,we investigated the correlations of nectin-4 and EMT-related proteins,as well as their correlations with clinicopathologic features.We designed the nectin-4 interference targeting RNA sequence,and transfected into gastric cancer cell line SGC7901.Western blot was applied to detect the expressions of nectin-4 and EMT-related proteins in gastric cancer cells SGC7901(group Con,group NC and group siRNA).Transwell chamber invasion assay was used to analyze the effect of nectin-4 on the invasion ability of gastric cancer cell SGC7901.Results:(1)The nectin-4 mRNA and proteins expressions were elevated in gastric cancer tissues compared to the adjacent normal gastric mucosas;the expressions of nectin-4,Snail and Vimentin in gastric cancer tissues were markedly higher compared to those in pericarcinous tissues;E-cadherin showed significantly lower expression in gastric cancer tissues.(2)The expression levels of nectin-4 and EMT-related proteins were closely correlated with T stage,lymph node metastasis and pTNM stage of gastric cancers.(3)The expression level of nectin-4 was positively correlated with those of Snail and Vimentin,but negatively correlated with E-cadherin expression in gastric cancer tissues.(4)Knockdown of nectin-4 upregualted the expression level of E-cadherin,and downregulated the expressions levels of Snail and Vimentin in gastric cancer cell line SGC7901,which significantly decreased the invasion ability of gastric cancer cell SGC7901.Conclusion: Nectin-4 played an important role in the advancement of gastric cancer,and probably promoting the invasion and metastasis of gastric cancer via the regulation of EMT.