Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-020-18951-2
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Funding
- Cancer Research UK (CRUK) [C33043/A12065, C33043/A24478, C48390/A21153, C30122/A11527, C30122/A15774]
- Royal Society [RG110591]
- Barts Charity
- Fundacion Alfonso Martin Escudero [659022]
- Marie Sklodowska-Curie Action [659022]
- MRC [C97993H, FC001112, MR/L023091/1]
- Harry J. Lloyd Charitable Trust
- Francis Crick Institute from CRUK [FC001112]
- Wellcome Trust [FC001112]
- CRUK/EPSRC [WT 203148/Z/16/Z]
- Wellcome Trust/EPSRC [WT 203148/Z/16/Z]
- NIHR BRC at Guy's and St Thomas' NHS Foundation Trust
- KCL [IS-BRC-1215-20006]
- CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland [ECMC C10355/A15587]
- ISCIII/FEDER Una manera de hacer Europa [FIS-PI1500711, PI18/00573]
- CIBERONC [CB16/12/0023]
- Marie Curie Actions (MSCA) [659022] Funding Source: Marie Curie Actions (MSCA)
- MRC [MR/L023091/1] Funding Source: UKRI
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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. Amoeboid cells are associated with melanoma invasive capacity. Here, the authors show that the WNT11-FZD7-DAAM1 pathway regulates tumour-initiating potential, invasion and metastasis lead by amoeboid cells in the invasive front of melanoma tumours.
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