SHP2 介导IL-6 促进乳腺癌细胞侵袭作用机制的研究*

目的:探讨非受体型酪氨酸磷酸酶SHP 2 介导白细胞介素- 6（interleukin- 6 ，IL- 6）促进人乳腺癌细胞侵袭的作用，以及相应的分子机制。方法:利用外源性重组IL- 6 处理人乳腺癌细胞T 47D ，采用表达IL- 6 的慢病毒感染T 47D 细胞使其内源性表达IL- 6，观察细胞的形态学改变情况，分析细胞迁移和侵袭能力的变化。采用小RNA 干扰的方法下调IL- 6 信号通路中关键分子SHP 2 的表达，观察其表达下降对IL- 6 促进乳腺癌细胞侵袭能力的影响，同时采用Westernblot方法检测Erk1/ 2 磷酸化变化。结果:上调IL- 6 在乳腺癌细胞中的表达显著促进乳腺癌细胞的迁移和侵袭能力，且细胞发生由上皮形态向类成纤维细胞形态的变化，同时伴随着上皮标志性蛋白E-cadherin 表达下调和间质标志Vimentin 表达上调。下调SHP 2 的表达明显抑制IL- 6 诱导乳腺癌细胞的上皮间质转化（epithelialmesenchymaltransition，EMT ）和侵袭能力，同时伴随着细胞内Erk1/ 2 磷酸化水平的下降。结论:SHP 2 通过介导IL- 6 诱导的EMT 促进乳腺癌细胞的迁移和侵袭能力。 

SHP2 mediates IL-6-induced enhancement of breast cancer cell invasiveness

Objective:To investigate the effect of non-receptor protein tyrosine phosphatase, SHP2, on the regulation of IL-6-induced invasiveness of breast cancer cells as well as its molecular mechanism. Methods:Human breast cancer cells, T47D, were treated with exogenous IL-6 or infected with IL-6-expressing lentivirus. Changes in cell morphology were observed, and cell migration and invasion ability were analyzed. Small interference RNA method was used to downregulate the expression of SHP2, a key molecule in IL-6 path-way. Wound healing and Transwell methods were used to investigate the effect of SHP2 knockdown on cell migration and invasion, and Western blot method was used to examine the changes of Erk1/2 phosphorylation. Results:Upregulation of IL-6 significantly en-hances migration and invasion of breast cancer cells. IL-6 induced a significant morphological switch from the epithelial phenotype to the mesenchymal fibroblast phenotype, downregulation of the epithelial marker E-cadherin, and upregulation of mesenchymal mark-er vimentin. Knockdown of SHP2 inhibited IL-6-induced epithelial mesenchymal transition and invasiveness. Phosphorylation of Erk1/2 also decreased in SHP2-silencing cells. Conclusion:SHP2 mediates IL-6-induced epithelial to mesenchymal transition and promotes in-vasiveness of breast cancer cells.