Syndecan-1 and -4 differentially regulate oncogenic K-ras dependent cell invasion into collagen through α2ß1 integrin and MT1-MMP.
Matrix Biol
; 30(3): 207-17, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21414405
ABSTRACT
Syndecans function as co-receptors for integrins on different matrixes. Recently, syndecan-1 has been shown to be important for α2ß1 integrin-mediated adhesion to collagen in tumor cells by regulating cell adhesion and migration on two-dimensional collagen. However, the function of syndecans in supporting α2ß1 integrin interactions with three-dimensional (3D) collagen is less well studied. Using loss-of-function and overexpression experiments we show that in 3D collagen syndecan-4 supports α2ß1-mediated collagen matrix contraction. Cell invasion through type I collagen containing 3D extracellular matrix (ECM) is driven by α2ß1 integrin and membrane type-1 matrix metalloproteinase (MT1-MMP). Here we show that mutational activation of K-ras correlates with increased expression of α2ß1 integrin, MT1-MMP, syndecan-1, and syndecan-4. While K-ras-induced α2ß1 integrin and MT1-MMP are positive regulators of invasion, silencing and overexpression of syndecans demonstrate that these proteins inhibit cell invasion into collagen. Taken together, these data demonstrate the existence of a complex interplay between integrin α2ß1, MT1-MMP, and syndecans in the invasion of K-ras mutant cells in 3D collagen that may represent a mechanism by which tumor cells become more invasive and metastatic.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteína Oncogénica p21(ras)
/
Movimiento Celular
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Colágeno
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Integrina alfa2beta1
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Metaloproteinasa 14 de la Matriz
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Sindecano-1
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Sindecano-4
Límite:
Humans
Idioma:
En
Revista:
Matrix Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Finlandia