Rab25 associates with α5β1 integrin to promote invasive migration in 3D microenvironments
Rab25 associates with α5β1 integrin to promote invasive migration in 3D microenvironments
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DOI：
10.1016/j.devcel.2007.08.012
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发表时间：
2007-10-01
影响因子：
11.8
通讯作者：
Norman, Jim C.
中科院分区：
文献类型：
--
作者：
Caswell, Patrick T.;Spence, Heather J.;Norman, Jim C.
在这里，我们报道了β 1整合素细胞质尾部与Rab25之间的直接相互作用，Rab25是一种与肿瘤侵袭性和转移有关的GTPase。Rab25促进了3D基质上的迁移模式，其特征是长伪足的延伸，GTPase与α 5 β 1的关联促进了将整合素运送到伪足尖端质膜的囊泡的定位，以及在细胞前部保留了一池循环α 5 β 1。此外，Rab25驱动的肿瘤细胞侵入三维细胞外基质环境强烈依赖于α 5 β 1整合素连接纤维连接蛋白以及Rab25与β 1整合素相互作用的能力。这些数据表明，Rab25通过指导整合素回收囊泡的定位，从而增强肿瘤细胞侵袭细胞外基质的能力，从而促进肿瘤的进展。
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.