Expression level of EGFR and MET receptors regulates invasiveness of melanoma cells

Abstract

Epidermal and hepatocyte growth factors can stimulate invasive abilities of melanoma cells, while treatment with combination of their receptors' (EGFR and MET, respectively) inhibitors reduces viability of these cells, as we have previously shown. Proposed therapy has potential; however, used drugs block more than one goal effectively, what raises the question about the real target of analysed inhibitors. For this reason, we analysed direct involvement of these receptors in the invasion of melanoma cells inducing EGFR and MET up- and down-regulations in examined cells. Results were acquired with assays evaluating cell migration and invasion (scratch wound assay, Transwell filter-based method and single-cell tracking). We revealed that cells' motile abilities are increased after EGFR overexpression and decreased following EGFR and MET silencing. This outcome correlates with elevated (EGFR up-regulation) or reduced (EGFR/MET down-regulation) number of formed invadopodia, visualized with immunofluorescence, and their rate of proteolytic abilities, evaluated by fluorescent gelatin degradation assay, and gelatin zymography, compared to control cells. Above-mentioned data indicate that both-EGFR and MET signalling is directly connected with melanoma cells invasion, what establishes these receptors as promising targets for anti-cancer treatment.

Keywords: EGFR; MET; invadopodia; invasion; melanoma.