c-erbB-2/EGFR as dominant heterodimerization partners determine a motogenic phenotype in human breast cancer cells

Separate mechanisms for oncogenesis and metastasis have been postulated. We show here that prolonged and invasive cell migration, a key mechanism in c ancer metastasis, is linked to c-erbB-2 signaling. Cell lines with c-erbB-2 and EGFR expression and transphosphorylation activity display a high trans endothelial invasiveness in an endothelial-extracellular matrix model mimic king a capillary vessel wall, in vitro. Tyrosine-phosphorylated c-erbB-2 re ceptors and EGFR are localized predominantly in areas of the cell with high membrane extension activity. On the molecular level, there is a subtle cro ss talk between the transmembrane signaling molecule c-erbB-2 and the actin cytoskeleton at multiple levels, including the generation of the second me ssenger PIP2 and the mobilization of the actin-regulatory protein gelsolin. Our data strongly suggest that c-erbB-2, especially in a heterodimer with EGFR, is closely involved in signaling pathways, inducing alterations in ce ll morphology that are required for a human breast cancer cell to become mo tile and conceivably metastatic.-Brandt, B. H., Roetger, A., Dittmar, T., N ikolai, G., Seeling, M., Merschjann, A., Nofer, J.-R., Dehmer-Moller, G., J unker, R., Assmann, G., Zaenker. K. S. c-erbB-2/EGFR as dominant heterodime rization partners determine a motogenic phenotype in human breast cancer ce lls.