Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells
AbstractAccumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors. However, whether Shp2 is involved in IL-6-signaling-promoted breast cancer EMT and progression, remains undefined. In this study, we showed that exogenous and endogenous IL-6 can enhance breast cancer invasion and migration, through the promotion of EMT. IL-6 also induces the activation of Erk1/2 and the phosphorylation of Shp2. Knockdown of Shp2 attenuated the IL-6-induced downregulation of E-cadherin, as well as IL-6-promoted cell migration and invasion. Moreover, by using Shp2 phosphatase mutants, phosphor-tyrosine mimicking, and deficiency mutants, we provided evidence that the phosphatase activity of Shp2 and its tyrosine phosphorylation, are necessary for the IL-6-induced downregulation of E-cadherin and the phosphorylation of Erk1/2. Our findings uncover an important function that links Shp2 to IL-6-promoted breast cancer progression. View Full-Text
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Sun, X.; Zhang, J.; Wang, Z.; Ji, W.; Tian, R.; Zhang, F.; Niu, R. Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells. Int. J. Mol. Sci. 2017, 18, 395.
Sun X, Zhang J, Wang Z, Ji W, Tian R, Zhang F, Niu R. Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells. International Journal of Molecular Sciences. 2017; 18(2):395.Chicago/Turabian Style
Sun, Xuan; Zhang, Jie; Wang, Zhiyong; Ji, Wei; Tian, Ran; Zhang, Fei; Niu, Ruifang. 2017. "Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells." Int. J. Mol. Sci. 18, no. 2: 395.
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