MCP-1-induced ERK/GSK-3β/Snail signaling facilitates the epithelial-mesenchymal transition and promotes the migration of MCF-7 human breast carcinoma cells.

Abstract

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-3β 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-3β 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-3β/Snail pathway, and identified a potential novel target for therapeutic intervention in breast cancer.

• Authors: Shun Li, Juan Lu, Yu Chen, Niya Xiong, Li Li, Jing Zhang, Hong Yang, Chunhui Wu, Hongjuan Zeng, Yiyao Liu
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 14 Issue 7 Pg. 621-630 (Jul 2017) ISSN: 2042-0226 [Electronic] China
• PMID: 26996066 (Publication Type: Journal Article)

Chemical References

• Chemokine CCL2
• Snail Family Transcription Factors
• Vascular Endothelial Growth Factor A
• Glycogen Synthase Kinase 3 beta
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase Kinases
• Matrix Metalloproteinases

Topics

• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Transformation, Neoplastic
• Chemokine CCL2 (pharmacology)
• Epithelial-Mesenchymal Transition (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• MCF-7 Cells
• Matrix Metalloproteinases (metabolism)
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Models, Biological
• Neoplasm Invasiveness
• Phenotype
• Phosphorylation (drug effects)
• Signal Transduction (drug effects)
• Snail Family Transcription Factors (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)