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3β1 integrins regulate CD151 complex assembly and membrane dynamics in carcinoma cells within 3D environments

Lookup NU author(s): Professor Boguslaw ObaraORCiD

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Abstract

Integrins are extracellular matrix (ECM) receptors that are key players in the regulation of tumour cell invasion. The laminin-binding integrin 3β1 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 3β1 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 3β1-CD151 binding correlates with lower CD151 homodimerisation in cells migrating on laminin or within matrigel. Loss of 3β1 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, 3-silenced cells show decreased actin-based membrane protrusion and retraction in both 2D and 3D environments. These data demonstrate that associations between 3β1 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. © 2013 Macmillan Publishers Limited All rights reserved.

Publication metadata

Author(s): Scales TME, Jayo A, Obara B, Holt MR, Hotchin NA, Berditchevski F, Parsons M

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2013

Volume: 32

Issue: 34

Pages: 3965-3979

Print publication date: 22/08/2013

Online publication date: 17/09/2012

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594

Publisher: Springer

URL: https://doi.org/10.1038/onc.2012.415

DOI: 10.1038/onc.2012.415

PubMed id: 22986527

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