Integrin β1 Is A Critical Effector In Promoting Metastasis And Chemo-resistance Of Esophageal Squamous Cell Carcinoma

ObjectiveTo downregulate ITGB1 expression in esophageal squamous cell carcinoma(ESCC)cells by lentivirus infection to explore the role of ITGB1 in metastasis and chemo-resistance of ESCC.Methodswe ascertained the expression pattern of ITGB1 in 29 pairs matched ESCC tissues and adjacent noncancerous tissues by realtime fluorescence quantitative PCR(RT-PCR).The mRNA expression level of ITGB1 was examined in ESCC cell lines.The packed lentiviral vector was transfected into ESCC cells and ITGB1 expression was detected by RT-PCR.Migration and invasion were evaluated by the transwell and wound healing assays.Two in vivo murine models(the pulmonary metastasis model and popliteal lymph node metastasis model)were used to evaluate the effect of ITGB1 blockage on the metastasis of ESCC cells.Cellular apoptosis was assessed by flow cytometry assay.To assess the effect of ITGB1 deletion on the sensitivity to DDP,ESCC cells were subcutaneously injected into Balb/c nude mice.The immunohistochemistry was used to assess the correlation between ITGB1 expression and clinical-pathological parameters.Western blot was used to analyze the interaction between ITGB1 and FAK signaling.ResultThe ITGB1 mRNA expression was higher in cancerous tissues compared with in adjacent normal tissue in 29 paired ESCC tissues.Mining two available expression datasets(GSE23400 and GSE20347)in Gene Expression Omnibus further validated that ITGB1 mRNA expression was elevated in malignant esophageal specimens.IHC staining of ESCC specimens(N=88)showed higher protein levels of ITGB1 in the cancerous epithelium than in normal tissue.Interestingly,aberrantly increased ITGB1 expression was signifcantly associated with lymph node metastasis and advanced stage ESCC in patients.ITGB1 defciency suppresses the motility of ESCC cells in vitro.Knockdown of ITGB1 impedes metastasis of ESCC cells in vivo.Depletion of ITGB1 inhibits the motility of ESCC cells by deactivating the FAK-Racl pathway.ITGB1 deficiency sensitizes ESCC cells to DDP.ConclusionsITGB1 plays an important role in metastasis and chemo-resistance of ESCC and contributes to a potential therapeutic treatment of ESCC.