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Updated: May 14, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Dasatinib inhibits primary melanoma cell proliferation through morphology-dependent disruption of Src-ERK signaling
Jianghong Wu1, Xin Liao, Bo Yu
1Department of Gastric Cancer and Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032; ; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032;
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.
Insights
Dasatinib treatment alters melanoma cell appearance and reduces proliferation by inhibiting the ERK signaling pathway. This suggests a role for Src in melanoma growth via this pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Advanced melanoma requires novel treatment strategies.
- The RAS/RAF/MAPK pathway and c-Src are frequently deregulated in melanoma.
- These pathways are implicated in melanoma development and progression.
Purpose of the Study:
- To investigate the functional interaction between c-Src and the MAPK pathway in melanoma.
- To determine the effect of dasatinib on melanoma cell proliferation and morphology.
- To elucidate the downstream signaling events affected by dasatinib.
Main Methods:
- Treatment of primary melanoma cells with dasatinib.
- Assessment of changes in cell morphology.
- Analysis of nuclear translocation of activated ERK1/2.
Main Results:
- Dasatinib induced significant changes in melanoma cell morphology, including arborization and contraction.
- A reduction in primary melanoma cell proliferation was observed following dasatinib treatment.
- Dasatinib treatment inhibited the nuclear translocation of activated ERK1/2.
Conclusions:
- Src signaling pathway activation, potentially through ERK1/2, promotes melanoma cell proliferation.
- Dasatinib's effects on cell morphology and proliferation are linked to the inhibition of ERK1/2 nuclear translocation.
- Targeting Src and its downstream pathways may offer a therapeutic strategy for advanced melanoma.
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