Dasatinib inhibits primary melanoma cell proliferation through morphology-dependent disruption of Src-ERK signaling

Abstract

New strategies for the treatment of advanced melanoma are urgently required. The RAS/RAF/MAPK pathway and c-Src are deregulated in the majority of malignant melanomas, suggesting that they may interact functionally and are involved in the development and progression of the malignancy. Preclinical studies have demonstrated variable inhibition of melanoma cell growth by dasatinib in vitro. Src may act through different downstream signaling pathways. In the present study, we demonstrate that dasatinib induces changes in cell morphology, characterized by an arborized and contracted appearance, and accompanied by a reduction in cell proliferation in primary melanoma cells. This morphological change is demonstrated to be associated with the inhibition of nuclear translocation of activated ERK1/2. Together, these results indicate that Src may promote cell proliferation through the activation of the ERK signaling pathway in melanoma oncogenesis.