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

TY - JOUR

T1 - Rab25 associates with alpha 5 beta 1 integrin to promote invasive migration in 3D microenvironments

AU - Caswell, P T

AU - Spence, H J

AU - Parsons, M

AU - White, D P

AU - Clark, K

AU - Cheng, K W

AU - Mills, G B

AU - Humphries, M J

AU - Messent, A J

AU - Anderson, K I

AU - McCaffrey, M W

AU - Ozanne, B W

AU - Norman, J C

PY - 2007/10/9

Y1 - 2007/10/9

N2 - 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

AB - 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

U2 - 10.1016/j.devcel.2007.08.012

DO - 10.1016/j.devcel.2007.08.012

M3 - Article

SN - 1878-1551

VL - 13

SP - 496

EP - 510

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -