WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion
More about Open Access at the CrickAuthors list
Irene Rodriguez-Hernandez Oscar Maiques Leonie Kohlhammer Gaia Cantelli Anna Perdrix Rosell Joanne Monger Bruce Fanshawe Vicky 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-MorenoAbstract
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.
Journal details
Journal Nature Communications
Volume 11
Issue number 1
Pages 5315
Available online
Publication date
Full text links
Publisher website (DOI) 10.1038/s41467-020-18951-2
Figshare View on figshare
Europe PubMed Central 33082334
Pubmed 33082334
Keywords
Related topics
Type of publication