| 1 | MCP-1-induced ERK/GSK-3β/Snail signaling facilitates the epithelial-mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells显示文摘Monocyte chemoattractant protein-1(MCP-1)is a chemotactic cytokine that can bind to its receptor cysteine-cysteine chemokine receptor 2(CCR2)and plays an important role in breast cancer cell metastasis.However,the molecular mechanisms underlying MCP-1-induced alterations in cellular functions during tumor progression are poorly understood.Here,we showed that MCP-1 stimulated the epithelial-mesenchymal transition(EMT)and induced the tumorigenesis of breast cancer cells by downregulating E-cadherin,upregulating vimentin and fibronectin,activating matrix metallopeptidase-2(MMP-2),and promoting migration and invasion.Moreover,MCP-1 treatment reduced glycogen synthase kinase-3β(GSK-3β)activity via the MEK/ERK-mediated phosphorylation of serine-9 in MCF-7 cells.The inhibition of MEK/ERK by U0126 attenuated the MCP-1-induced phosphorylation of GSK-3βand decreased the expression of Snail,an EMT-related transcription factor,leading to the inhibition of MCF-7 cell migration and invasion.Inactivation of GSK-3βby LiCl(lithium chloride)treatment notably increased MMP-2 activity,vascular endothelial growth factor expression and EMT of MCF-7 cells.These findings revealed that MCP-1-induced EMT and migration are mediated by the ERK/GSK-3β/Snail pathway,and identified a potential novel target for therapeutic intervention in breast cancer. | Shun Li Juan Lu Yu Chen Niya Xiong Li Li Jing Zhang Hong Yang Chunhui Wu Hongjuan Zeng Yiyao Liu | 2017 | Cellular & Molecular Immunology2017，14，7： | 14 |
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