WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion

Irene Rodriguez-Hernandez, Oscar Maiques, Leonie Kohlhammer, Gaia Cantelli, Anna Perdrix-Rosell, Joanne Monger, Bruce Fanshawe, Victoria L Bridgeman, Sophia N Karagiannis, Rosa M Penin, Joaquim Marcolval, Rosa M Marti, Xavier Matias-Guiu, Gilbert O Fruhwirth, Jose L Orgaz, Ilaria Malanchi, Victoria Sanz-Moreno

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)
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Abstract

Melanoma is a highly aggressive tumour that can metastasize very early in disease progression. Notably, melanoma can disseminate using amoeboid invasive strategies. We show here that high Myosin II activity, high levels of ki-67 and high tumour-initiating abilities are characteristic of invasive amoeboid melanoma cells. Mechanistically, we find that WNT11-FZD7-DAAM1 activates Rho-ROCK1/2-Myosin II and plays a crucial role in regulating tumour-initiating potential, local invasion and distant metastasis formation. Importantly, amoeboid melanoma cells express both proliferative and invasive gene signatures. As such, invasive fronts of human and mouse melanomas are enriched in amoeboid cells that are also ki-67 positive. This pattern is further enhanced in metastatic lesions. We propose eradication of amoeboid melanoma cells after surgical removal as a therapeutic strategy.

Original languageEnglish
Article number5315
Pages (from-to)5315
JournalNature Communications
Volume11
Issue number1
Early online date20 Oct 2020
DOIs
Publication statusPublished - 1 Dec 2020

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