The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA.
The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA.
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DOI：
10.1083/jcb.200709076
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发表时间：
2008-06-16
期刊：
影响因子：
--
通讯作者：
Chavrier P
中科院分区：
文献类型：
--
作者：
Sakurai-Yageta M;Recchi C;Le Dez G;Sibarita JB;Daviet L;Camonis J;D'Souza-Schorey C;Chavrier P
侵袭伪足是在侵袭性肿瘤细胞和具有基质蛋白水解活性的细胞外基质之间的接触部位形成的基于肌动蛋白的膜突起。肌动蛋白调节蛋白参与侵袭伪足的形成，而基质降解需要靶向侵袭伪足的金属蛋白酶（MMPs）。在这项研究中，我们表明，囊泡栓系外囊复合物是必要的基质蛋白水解和乳腺癌细胞的侵袭。我们证明，外囊亚基Sec3和Sec8与极性蛋白IQGAP 1相互作用，这种相互作用是由活性Cdc42和RhoA触发的，这是基质降解所必需的。IQGAP 1和外囊之间的相互作用是侵袭伪足活性所必需的，因为IQGAP 1表达诱导的基质降解增强在外囊结合位点缺失后丧失。我们进一步表明，外囊和IQGAP 1所需的细胞表面膜1型MMP在侵袭伪足的积累。基于这些结果，我们提出肿瘤细胞中的侵袭伪足功能依赖于Rho鸟苷三磷酸酶下游的细胞骨架组装和胞吐作用的协调。
Invadopodia are actin-based membrane protrusions formed at contact sites between invasive tumor cells and the extracellular matrix with matrix proteolytic activity. Actin regulatory proteins participate in invadopodia formation, whereas matrix degradation requires metalloproteinases (MMPs) targeted to invadopodia. In this study, we show that the vesicle-tethering exocyst complex is required for matrix proteolysis and invasion of breast carcinoma cells. We demonstrate that the exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. Interaction between IQGAP1 and the exocyst is necessary for invadopodia activity because enhancement of matrix degradation induced by the expression of IQGAP1 is lost upon deletion of the exocyst-binding site. We further show that the exocyst and IQGAP1 are required for the accumulation of cell surface membrane type 1 MMP at invadopodia. Based on these results, we propose that invadopodia function in tumor cells relies on the coordination of cytoskeletal assembly and exocytosis downstream of Rho guanosine triphosphatases.
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