De Winde, Charlotte;
George, Samantha;
Arp, Abbey;
Benjamin, Agnesska;
Crosas-Molist, Eva;
Hari-Gupta, Yukti;
Carver, Alexander;
... Acton, Sophie; + view all
(2020)
Podoplanin drives dedifferentiation and amoeboid invasion of melanoma.
BioRxiv: Cold Spring Harbor, NY, USA.
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Abstract
Melanoma is an aggressive skin cancer developing from melanocytes, 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 enhances amoeboid invasion in melanoma. Expression of podoplanin in murine melanoma models drives rounded cell morphology, increasing motility and invasion in vivo. Podoplanin expression is upregulated in a subset of dedifferentiated human melanoma, and in vitro is sufficient to suppress melanogenesis and upregulate melanoma-associated markers Mitf and Pou3f2. Together, our data indicates that podoplanin is both a potential biomarker for dedifferentiated invasive melanoma and a promising migrastatic therapeutic target.
| Type: | Working / discussion paper |
|---|---|
| Title: | Podoplanin drives dedifferentiation and amoeboid invasion of melanoma |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/2020.07.23.218578 |
| Publisher version: | https://doi.org/10.1101/2020.07.23.218578 |
| Language: | English |
| Additional information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | Metastasis, Podoplanin, Melanoma, Amoeboid, Dedifferentiation |
| 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 > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10180828 |
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