Epithelial‐to‐mesenchymal‐like transition events in melanoma

• Published in: The FEBS journal 2022-03, Vol.289 (5), p.1352-1368
• Main Authors: Pedri, Dennis, Karras, Panagiotis, Landeloos, Ewout, Marine, Jean‐Christophe, Rambow, Florian
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cell Differentiation - drug effects; Comparative analysis; Drug Resistance, Neoplasm - genetics; EMT; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Epithelial-Mesenchymal Transition - drug effects; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic; Humans; Melanoma; Melanoma - drug therapy; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mesenchymal Stem Cells - pathology; Mesenchyme; Metastases; Metastasis; Molecular Targeted Therapy - methods; Neoplasm Metastasis; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; phenotype switching; Skin Neoplasms - drug therapy; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor cells; Tumors
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.16021

Epithelial‐to‐mesenchymal transition (EMT), a process through which epithelial tumor cells acquire mesenchymal phenotypic properties, contributes to both metastatic dissemination and therapy resistance in cancer. Accumulating evidence indicates that nonepithelial tumors, including melanoma, can also gain mesenchymal‐like properties that increase their metastatic propensity and decrease their sensitivity to therapy. In this review, we discuss recent findings, illustrating the striking similarities—but also knowledge gaps—between the biology of mesenchymal‐like state(s) in melanoma and mesenchymal state(s) from epithelial cancers. Based on this comparative analysis, we suggest hypothesis‐driven experimental approaches to further deepen our understanding of the EMT‐like process in melanoma and how such investigations may pave the way towards the identification of clinically relevant biomarkers for prognosis and new therapeutic strategies. Epithelial‐to‐mesenchymal transition (EMT) allows epithelial tumor cells to acquire mesenchymal phenotypic properties to metastasize and resist drug treatment. Melanoma cells undergo a process called phenotype switching, that strikingly resembles EMT, both in phenotypic characteristics and molecular mechanisms. In this review, we highlight both similarities and differences between EMT and phenotype switching, identifying knowledge gaps in the field and proposing experimental approaches to investigate this key phenomenon.