三阴性乳腺癌组织中AIF1L低表达及其抑制癌细胞增殖、迁移、侵袭的机制探讨

Low expression of AIF1L in triple negative breast cancer tissues and its mechanism of inhibiting proliferation,migration and invasion of cancer cells

目的:探究三阴性乳腺癌(triple negative breast cancer,TNBC)组织中同种异体移植炎症因子1样(allograft inflammatory factor-1 like,AIF1L)的表达及其对癌细胞增殖、迁移、侵袭的影响和分子机制。方法:分别选取132例乳腺癌组织和39例癌旁组织标本以及TNBC细胞系MDAMB231进行研究。采用免疫组化染色法验证乳腺癌不同分子分型中AIF1L表达情况。通过构建过表达AIF1L腺病毒载体转染MDAMB231细胞系,采用MTT实验、细胞划痕愈合实验、Transwell实验、细胞伸展实验分别检测AIF1L对TNBC细胞增殖、迁移、侵袭及伸展能力的影响;采用Western blot法检测AIF1L对FAK-RhoA信号通路及上皮间质转化(epithelial mesenchymal transition,EMT)的影响,探究其分子作用机制。结果:乳腺癌组织中AIF1L阳性表达率低于癌旁组织,TNBC组织中AIF1L阳性表达率最低。AIF1L抑制MDAMB231细胞的增殖、迁移、侵袭及伸展能力。AIF1L抑制FAK-RhoA信号通路相关蛋白表达及活性,逆转癌细胞EMT表型。结论:AIF1L在TNBC组织中极低表达,对TNBC细胞生物学功能具有抑制作用,其可能是通过抑制FAK-RhoA信号通路和(或)EMT相关通路进而抑制肿瘤细胞的迁移、侵袭。

Objective:To explore the expression of AIF1L in triple negative breast cancer(TNBC)tissues and its effect on proliferation,migration and invasion of cancer cells and its molecular mechanism.Methods:132 cases of breast cancer tissues and 39 cases of paracancer tissues as well as TNBC cell line MDAMB231 were selected for study.Immunohistochemical staining was used to verify the expression of AIF1L in breast cancer tissue different molecular types.The overexpressed AIF1L adenovirus vector was constructed and transfected into MDAMB231 cell lines.The effects of AIF1L on the proliferation,migration,invasion and extension of TNBC cells were detected by MTT assay,cell scratch healing assay,Transwell assay and cell extension assay.Western blot was used to detect the effect of AIF1L on FAK-RhoA signaling pathway and EMT,and to explore the molecular mechanism.Results:The positive expression rate of AIF1L in breast cancer tissues was lower than that in adjacent tissues,and the positive expression rate of AIF1L in TNBC tissues was the lowest.AIF1L inhibited the proliferation,migration,invasion and extension of MDAMB231 cells.AIF1L inhibited the expression and activity of FAK-RhoA signaling pathway,and reversed the EMT phenotype of cancer cells.Conclusion:The expression of AIF1L in TNBC tissues is extremely low,which has an inhibitory effect on the biological function of TNBC cells.It may be that AIF1L inhibits the migration and invasion of tumor cells by inhibiting the FAK-RhoA signaling pathway and/or EMT-related pathways.