EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells.
The mechanisms by which cancer cells migrate to metastasise are not fully understood. Breast cancers are accompanied by electrical depolarisation of tumour epithelial cells. The electrical changes can be detected on the skin and are used to differentiate malignant from benign breast tumours. Could the electrical signals play a role in metastasis by promoting tumour cell migration? We report that electric fields stimulate and direct migration of human breast cancer cells. Importantly, these effects were more significant in highly metastatic tumour cells than in low metastatic tumour cells. Electric-field-enhanced directional migration correlates well with the expression level of EGF receptor (EGFR/ErbB1). To confirm this, we transfected low metastatic clone MTC cells with human ErbB1, which significantly increased the electrotactic response. Inhibition of ErbB1 completely abolished the directional response of MTLn3 cells to an electric field. Transfection of MTLn3 cells and MDA-MB-435 cells with expression vectors for ErbB family members ErbB1, ErbB2 and ErbB3 also significantly enhanced EF-induced migration. These results suggest that electric signals might play a role in metastasis of breast cancers by enhancing cell migration through the ErbB-signalling pathway.
Pu
Jin
J
School of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
McCaig
Colin D
CD
Cao
Lin
L
Zhao
Zhiqiang
Z
Segall
Jeffrey E
JE
Zhao
Min
M
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004560:Electricity; D004791:Enzyme Inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D020741:rho GTP-Binding Proteins