Dr Lotte de Winde

UCL

Podoplanin drives dedifferentiation and amoeboid invasion of melanoma

Melanoma is an aggressive skin cancer, frequently resulting in metastatic disease. Melanoma cells utilise amoeboid migration as mode of local invasion. Amoeboid invasion is characterized by rounded cell morphology and high actomyosin contractility driven by the RhoA signalling pathway. Migrastatic drugs targeting actin polymerization and contractility to inhibit invasion and metastasis are therefore a promising treatment option. To predict amoeboid invasion and metastatic potential there is a need for biomarkers functionally linked to contractility pathways. The glycoprotein podoplanin drives actomyosin contractility in lymphoid fibroblasts, and is overexpressed in several cancer types. Here, we show that podoplanin is a novel driver of amoeboid invasion in melanoma. Podoplanin expression is upregulated in human melanoma, and expression of podoplanin in murine melanoma models drives rounded cell morphology, increasing motility and invasion in vivo. Furthermore podoplanin drives dedifferentiation of melanoma cells, reducing melanogenesis and upregulating motility. Together, our data shows that expression of podoplanin drives disease progression and could be a promising migrastatic therapeutic target in melanoma.

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