Journal
DEVELOPMENTAL CELL
Volume 13, Issue 4, Pages 496-510Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2007.08.012
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Funding
- Medical Research Council [G0100152] Funding Source: researchfish
- Medical Research Council [G0100152] Funding Source: Medline
- MRC [G0100152] Funding Source: UKRI
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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.
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