Slc7a11通过E-cadherin/β-catenin信号通路诱导自噬促进乳腺癌细胞侵袭转移的作用机制研究

Mechanism of SLC7A11 induced autophagy to promote invasion and metastasis of breast cancer cells via E-cadherin/β-catenin signal pathway

目的:探讨溶质载体家族7成员11(Solute carrier family7 member11,Slc7a11)对乳腺癌细胞侵袭转移的作用机制。方法:采用细胞划痕实验与Transwell实验检测Slc7a11对MDA-MB-231细胞迁移的影响,采用免疫印记(Western blotting,WB)检测Slc7a11对MDA-MB-231细胞黏附相关分子E-钙黏蛋白(Ecadherin)与β-连环蛋白(β-catenin)表达及自噬相关蛋白Beclin-1、LC3II和p62表达的影响。结果:与对照组比较,Slc7a11过表达组E-cadherin和β-catenin蛋白表达明显降低(P<0.05),细胞体外与迁移侵袭实验检测到,穿过Transwell小室的细胞数量明显升高(P<0.05)。与对照组比较,干扰Slc7a11表达组Ecadherin和β-catenin蛋白表达明显升高,细胞体外与迁移侵袭实验检测到,穿过Transwell小室的细胞数量明显降低(P<0.05)。过表达Slc7a11后,自噬相关基因包括Beclin-1和LC3II的表达明显上调,而p62表达明显降低(P<0.05)。结论:Slc7a11能够调控细胞自噬促进乳腺癌细胞侵袭和转移,其主要机制可能与其下调细胞黏附分子E-cadherin/β-catenin复合体表达有关。

Objective:To investigate the mechanism of Slc7a11 on invasion and metastasis of breast cancer cells.Methods:The effect of Slc7a11 on the migration of MDA-MB-231 cells was detected by cell scratch assay and transwell assay,western blotting was used to detect the effect of SLC7A11 on the expression of E-cadherin,β-Catenin,and the expression of autophagy related proteins Beclin-1,LC3II and p62.Results:Compared with the control group,E-cadherin andβ-catenin were decreased in overexpressing Slc7a11 group(P<0.05),and transwell cell migration and invasion assay in vitro detected an increase in the number of cells passing through the cell compartment(P<0.05).Compared with the control group,E-cadherin andβ-catenin were increased in short hairpin Slc7a11 group,and transwell cell migration and invasion assay in vitro detected a decrease in the number of cells passing through the cell compartment(P<0.05).After overexpression of Slc7a11,the expression of autophagy related genes including Beclin-1 and LC3II was up-regulated,while the expression of p62 was decreased(P<0.05).Conclusion:Slc7a11 can regulate autophagy and promote the invasion and metastasis of breast cancer cells,and its main mechanism may be the down regulation of cell adhesion molecule E-cadherin/β-catenin complex expression.