PMID- 26996066 OWN - NLM STAT- MEDLINE DCOM- 20180326 LR - 20220321 IS - 2042-0226 (Electronic) IS - 1672-7681 (Print) IS - 1672-7681 (Linking) VI - 14 IP - 7 DP - 2017 Jul TI - MCP-1-induced ERK/GSK-3beta/Snail signaling facilitates the epithelial-mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells. PG - 621-630 LID - 10.1038/cmi.2015.106 [doi] AB - 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-3beta (GSK-3beta) 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-3beta and decreased the expression of Snail, an EMT-related transcription factor, leading to the inhibition of MCF-7 cell migration and invasion. Inactivation of GSK-3beta by 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-3beta/Snail pathway, and identified a potential novel target for therapeutic intervention in breast cancer. FAU - Li, Shun AU - Li S AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Lu, Juan AU - Lu J AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Chen, Yu AU - Chen Y AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Xiong, Niya AU - Xiong N AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Li, Li AU - Li L AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Zhang, Jing AU - Zhang J AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Yang, Hong AU - Yang H AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. AD - Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Wu, Chunhui AU - Wu C AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. AD - Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Zeng, Hongjuan AU - Zeng H AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. AD - Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. FAU - Liu, Yiyao AU - Liu Y AD - Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. AD - Center for Information in Biomedicine, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, China. LA - eng PT - Journal Article DEP - 20160321 PL - China TA - Cell Mol Immunol JT - Cellular & molecular immunology JID - 101242872 RN - 0 (Chemokine CCL2) RN - 0 (Snail Family Transcription Factors) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - EC 3.4.24.- (Matrix Metalloproteinases) SB - IM MH - Breast Neoplasms/*metabolism/*pathology MH - Cell Line, Tumor MH - Cell Movement/*drug effects MH - Cell Transformation, Neoplastic MH - Chemokine CCL2/*pharmacology MH - Epithelial-Mesenchymal Transition/*drug effects MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - Glycogen Synthase Kinase 3 beta/*metabolism MH - Humans MH - MCF-7 Cells MH - Matrix Metalloproteinases/metabolism MH - Mitogen-Activated Protein Kinase Kinases/metabolism MH - Models, Biological MH - Neoplasm Invasiveness MH - Phenotype MH - Phosphorylation/drug effects MH - Signal Transduction/drug effects MH - Snail Family Transcription Factors/*metabolism MH - Vascular Endothelial Growth Factor A/metabolism PMC - PMC5520413 COIS- The authors declare no conflict of interest. EDAT- 2016/03/22 06:00 MHDA- 2018/03/27 06:00 PMCR- 2018/07/01 CRDT- 2016/03/22 06:00 PHST- 2015/10/14 00:00 [received] PHST- 2015/11/28 00:00 [revised] PHST- 2015/11/29 00:00 [accepted] PHST- 2016/03/22 06:00 [pubmed] PHST- 2018/03/27 06:00 [medline] PHST- 2016/03/22 06:00 [entrez] PHST- 2018/07/01 00:00 [pmc-release] AID - cmi2015106 [pii] AID - 10.1038/cmi.2015.106 [doi] PST - ppublish SO - Cell Mol Immunol. 2017 Jul;14(7):621-630. doi: 10.1038/cmi.2015.106. Epub 2016 Mar 21.