Abstract
The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50, also known as NHERF1 or NHERF) inhibits epidermal growth factor (EGF)-induced breast cancer cell proliferation after 3 days by blocking EGF receptor (EGFR) phosphorylation. The loss of EBP50 stimulates EGFR activity and induces the appearance of epithelial-to-mesenchymal transition phenotypic features in biliary cancer cells. However, the involvement of EBP50 in breast cancer migration and invasion remains unknown. We report that EBP50 inhibits the migration and invasion of breast cancer cells by inhibiting the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization mediating cytoskeletal rearrangement. Additionally, EGF-induced phosphorylation of Akt and mTOR was suppressed by upregulation of EBP50. Our results indicate that EBP50 is significantly involved in breast cancer invasion/metastasis via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway.
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Acknowledgments
This work was supported by The Young and Middle-Aged Scientists Research Awards Foundation of Shandong Province (BS2011YY060), Foundation of Shandong Educational Committee (J12LK03 and J13LK03).
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Hongli Li and Baogang Zhang contributed equally to this work.
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Li, H., Zhang, B., Liu, Y. et al. EBP50 inhibits the migration and invasion of human breast cancer cells via LIMK/cofilin and the PI3K/Akt/mTOR/MMP signaling pathway. Med Oncol 31, 162 (2014). https://doi.org/10.1007/s12032-014-0162-x
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DOI: https://doi.org/10.1007/s12032-014-0162-x