title: PI3K signalling is required for a TGFβ-induced epithelial-mesenchymal-like transition (EMT-like) in human melanoma cells.
abstract: 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 TGFβ exposure can induce a dedifferentiated EMT-like state resembling a previously described invasive phenotype (EMT-like). TGFβ-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 TGFβ-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.
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Schlegel
authors.forename: Anina
authors.initials: A
authors.lastname: von Planta
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Widmer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Christofori
mesh_terms: D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D019869:Phosphatidylinositol 3-Kinases
keywords: PDGF; epithelial−mesenchymal transition; melanoma; phosphoinositide-3-kinase; transforming growth factor β