Rab25 Mediates Integrin Recycling for Tumor Cell Migration in 3D

Abstract

Prior to the publication of this report, the importance of endocytotic and exocytotic recycling of integrins was just beginning to be recognized. However, the findings in this report provided significant new insights into the mechanisms mediating integrin recycling and the critical importance of spatially regulated recycling in controlling specific aspects of cell migration and invasion. The Rab family GTPase RAB25, which has been implicated in tumor progression, was found to bind directly to β1 integrin and, through this interaction, specifically deliver α5β1-containing vesicles to the tips of pseudopodial extensions. This RAB25-integrin interaction was found to be critical for directional invasion of tumor cells in 3D extracellular matrix environments. I liked this report not only for the elegance of the experiments and fundamental insights into matrix receptor recycling, but also because it provided mechanistic insights into how aberrant vesicle trafficking and receptor recycling could contribute to tumorigenesis. This PaperPick refers to Rab25 associates with α5β1 integrin to promote invasive migration in 3D microenvironments, by P.T. Caswell, H.J. Spence, M. Parsons, D.P. White, K. Clark, K.W. Cheng, G.B. Mills, M.J. Humphries, A.J. Messent, K.I. Anderson, M.W. McCaffrey, B.W. Ozanne, and J.C. Norman, published in October 2007. Video Abstract Jim Norman and Pat Caswell discuss their 2007 paper, in which they found that an interaction between a Rab GTPase and an integrin is important for cell migration and tumor metastasis.