Diverse matrix metalloproteinase functions regulate cancer amoeboid migration.
Nat Commun
; 5: 4255, 2014 Jun 25.
Article
em En
| MEDLINE
| ID: mdl-24963846
ABSTRACT
Rounded-amoeboid cancer cells use actomyosin contractility driven by Rho-ROCK and JAK-STAT3 to migrate efficiently. It has been suggested that rounded-amoeboid cancer cells do not require matrix metalloproteinases (MMPs) to invade. Here we compare MMP levels in rounded-amoeboid and elongated-mesenchymal melanoma cells. Surprisingly, we find that rounded-amoeboid melanoma cells secrete higher levels of several MMPs, including collagenase MMP-13 and gelatinase MMP-9. As a result, rounded-amoeboid melanoma cells degrade collagen I more efficiently than elongated-mesenchymal cells. Furthermore, using a non-catalytic mechanism, MMP-9 promotes rounded-amoeboid 3D migration through regulation of actomyosin contractility via CD44 receptor. MMP-9 is upregulated in a panel of rounded-amoeboid compared with elongated-mesenchymal melanoma cell lines and its levels are controlled by ROCK-JAK-STAT3 signalling. MMP-9 expression increases during melanoma progression and it is particularly prominent in the invasive fronts of lesions, correlating with cell roundness. Therefore, rounded-amoeboid cells use both catalytic and non-catalytic activities of MMPs for invasion.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Actomiosina
/
Movimento Celular
/
Metaloproteinase 9 da Matriz
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Fator de Transcrição STAT3
/
Metaloproteinase 13 da Matriz
/
Janus Quinases
/
Quinases Associadas a rho
/
Melanoma
Limite:
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2014
Tipo de documento:
Article