WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion.
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Embargo End Date
ICR Authors
Authors
Rodriguez-Hernandez, I
Maiques, O
Kohlhammer, L
Cantelli, G
Perdrix-Rosell, A
Monger, J
Fanshawe, B
Bridgeman, VL
Karagiannis, SN
Penin, RM
Marcolval, J
Marti, RM
Matias-Guiu, X
Fruhwirth, GO
Orgaz, JL
Malanchi, I
Sanz-Moreno, V
Maiques, O
Kohlhammer, L
Cantelli, G
Perdrix-Rosell, A
Monger, J
Fanshawe, B
Bridgeman, VL
Karagiannis, SN
Penin, RM
Marcolval, J
Marti, RM
Matias-Guiu, X
Fruhwirth, GO
Orgaz, JL
Malanchi, I
Sanz-Moreno, V
Document Type
Journal Article
Date
2020-10-20
Date Accepted
2020-09-14
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.
Citation
Nature Communications, 2020, 11 (1), pp. 5315 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723