α3ß1 integrins regulate CD151 complex assembly and membrane dynamics in carcinoma cells within 3D environments.
Oncogene
; 32(34): 3965-79, 2013 Aug 22.
Article
em En
| MEDLINE
| ID: mdl-22986527
ABSTRACT
Integrins are extracellular matrix (ECM) receptors that are key players in the regulation of tumour cell invasion. The laminin-binding integrin α3ß1 has previously been shown to regulate adhesion and migration of carcinoma cells in part through co-operative signalling with the tetraspanin family of transmembrane proteins. However, the spatial and temporal regulation of crosstalk between these families of transmembrane proteins in intact cells remains poorly understood. Here we have used fluorescence resonance energy transfer (FRET) to demonstrate for the first time that α3ß1 and the tetraspanin CD151 directly associate at the front and retracting rear of polarised migrating breast carcinoma cells in both two-dimentional (2D) and three-dimentional (3D)matrices. Furthermore, localised α3ß1-CD151 binding correlates with lower CD151 homodimerisation in cells migrating on laminin or within matrigel. Loss of α3ß1 integrin leads to increased CD151 homodimer formation, increased activation of Rho GTPase, loss of cell polarity and decreased invasion in 3D ECM. As a result, α3-silenced cells show decreased actin-based membrane protrusion and retraction in both 2D and 3D environments. These data demonstrate that associations between α3ß1 and CD151 occur dynamically within discrete subcellular compartments and act to establish local GTPase signalling to promote tumour cell invasion. These novel findings shed light on the complex crosstalk and switching between receptor complexes in response to different extracellular cues during cell invasion in 3D environments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
/
Técnicas de Cultura de Células
/
Integrina alfa3beta1
/
Tetraspanina 24
Limite:
Female
/
Humans
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Reino Unido