Journal
EXPERIMENTAL DERMATOLOGY
Volume 24, Issue 1, Pages 22-28Publisher
WILEY
DOI: 10.1111/exd.12580
Keywords
epithelial-mesenchymal transition; melanoma; PDGF; phosphoinositide-3-kinase; transforming growth factor beta
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Funding
- Swiss National Science Foundation [31003A_127476, 31003_144206]
- Swiss National Science Foundation (SNF) [31003A_127476] Funding Source: Swiss National Science Foundation (SNF)
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Epithelial to mesenchymal transition (EMT) is a programme defined in epithelial cells and recognized as playing a critical role in cancer progression. Although melanoma is not a cancer of epithelial cells, hallmarks of EMT have been described to play a critical role in melanoma progression. Here, we demonstrate that long-term TGF exposure can induce a dedifferentiated EMT-like state resembling a previously described invasive phenotype (EMT-like). TGF-induced EMT-like is marked by the downregulation of melanocyte differentiation markers, such as MITF, and the upregulation of mesenchymal markers, such as N-cadherin, and an increase in melanoma cell migration and cell invasion. Pharmacological interference shows the dependency of TGF-induced EMT-like on the activation of the PDGF signalling pathway and the subsequent activation of PI3K in human melanoma cells. Together, the data provide novel insights into the transcriptional plasticity of melanoma cells that might contribute to tumor progression in patients and propose avenues to therapeutic interventions.
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