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Podoplanin drives dedifferentiation and amoeboid invasion of melanoma

de Winde, CM; George, SL; Crosas-Molist, E; Hari-Gupta, Y; Arp, AB; Benjamin, AC; Millward, LJ; ... Acton, SE; + view all (2021) Podoplanin drives dedifferentiation and amoeboid invasion of melanoma. iScience , 24 (9) , Article 102976. 10.1016/j.isci.2021.102976. Green open access

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Abstract

Melanoma is an aggressive skin cancer developing from melanocytes, frequently resulting in metastatic disease. Melanoma cells utilize amoeboid migration as mode of local invasion. Amoeboid invasion is characterized by rounded cell morphology and high actomyosin contractility driven by Rho GTPase signalling. Migrastatic drugs targeting actin polymerization and contractility are therefore a promising treatment option for metastatic melanoma. To predict amoeboid invasion and metastatic potential, biomarkers functionally linked to contractility pathways are needed. The glycoprotein podoplanin drives actomyosin contractility in lymphoid fibroblasts and is overexpressed in many cancers. We show that podoplanin enhances amoeboid invasion in melanoma. Podoplanin expression in murine melanoma drives rounded cell morphology, increasing motility, and invasion in vivo. Podoplanin expression is increased in a subset of dedifferentiated human melanoma, and in vitro is sufficient to upregulate melanoma-associated marker Pou3f2/Brn2. Together, our data define podoplanin as a functional biomarker for dedifferentiated invasive melanoma and a promising migrastatic therapeutic target.

Type: Article
Title: Podoplanin drives dedifferentiation and amoeboid invasion of melanoma
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.isci.2021.102976
Publisher version: https://doi.org/10.1016/j.isci.2021.102976
Language: English
Additional information: © 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10133732
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