WNT11-FZD7-DAAM1 signalling supports tumour initiating abilities and melanoma amoeboid invasion.
Nat Commun
; 11(1): 5315, 2020 10 20.
Article
em En
| MEDLINE
| ID: mdl-33082334
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas rho de Ligação ao GTP
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Proteínas Wnt
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Receptores Frizzled
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Melanoma
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Proteínas dos Microfilamentos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article