Abstract

Breast cancer cells tend to first move into the lumen of the mammary ducts, where they proliferate. Then, after tissue deformation occurs, the cells breach the basement membrane and metastasize through the lymph and blood vessels. Pu et al . propose that the transepithelial potential, with the duct lumen having a relatively positive charge, creates an endogenous electric field that contributes to the movement of cancer cells. The authors used electric fields that were smaller than those that should exist across the breast duct epithelium based on the transepithelial potential to test whether breast cancer cell lines responded to the presence of such an electric field. The authors noted a correlation between the metastatic potential of human and rat mammary cancer cell lines and directional migration in the presence of an electric field (the cells moved toward the anode). The abundance of the epidermal growth factor receptor ErbB1 also correlated with directed migration in an electric field, and inhibition of ErbB1 with AG1478 profoundly reduced electric field-induced directed migration. Overexpression of ErbB1, ErbB2, or ErbB3 increased directed migration of two mammary tumor cell lines in response to an electric field. Pharmacological inhibitors were used to explore the signaling pathway responsible for migration, and tyrosine kinase activity, phosphatidylinositol 3-kinase, RhoA, Cdc42, and extracellular signal-regulated kinase (ERK) were all involved. J. Pu, C. D. McCaig, L. Cao, Z. Zhao, J. E. Segall, M. Zhao, EGF receptor signaling is essential for electric-field-directed migration of breast cancer cells. J. Cell Sci. 120 , 3395-3403 (2007). [Abstract] [Full Text]

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