Rab25 associates with alpha 5 beta 1 integrin to promote invasive migration in 3D microenvironments

Caswell, P. et al. (2007) Rab25 associates with alpha 5 beta 1 integrin to promote invasive migration in 3D microenvironments. Developmental Cell, 13(4), pp. 496-510. (doi: 10.1016/j.devcel.2007.08.012)

Abstract

Here, we report a direct interaction between the beta 1 integrin cytoplasmic tail and Rab25, a GTPase that has been linked to tumor aggressiveness and metastasis. Rab25 promotes a mode of migration on 3D matrices that is characterized by the extension of long pseudopodia, and the association of the GTPase with alpha 5 beta 1 promotes localization of vesicles that deliver integrin to the plasma membrane at pseudopodial tips as well as the retention of a pool of cycling alpha 5 beta 1 at the cell front. Furthermore, Rab25-driven tumor-cell invasion into a 3D extracellular matrix environment is strongly dependent on ligation of fibronectin by alpha 5 beta 1 integrin and the capacity of Rab25 to interact with beta 1 integrin. These data indicate that Rab25 contributes to tumor progression by directing the localization of integrin-recycling vesicles and thereby enhancing the ability of tumor cells to invade the extracellular matrix.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Anderson, Professor Kurt and Norman, Professor James and Caswell, Dr Patrick and Ozanne, Professor Bradford and White, Mr Dominic and Spence, Dr Heather
• Authors: Caswell, P., Spence, H., Parsons, M., White, D., Clark, K., Cheng, K., Mills, G., Humphries, M., Messent, A., Anderson, K., McCaffrey, M., Ozanne, B., and Norman, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Developmental Cell
• ISSN: 1534-5807