Differences in the localization of the APC-Asef/Asef2 complex between APC wild-type and mutant cells
Differences in the localization of the APC-Asef/Asef2 complex between APC wild-type and mutant cells
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APC 野生型和突变细胞之间 APC-Asef/Asef2 复合物定位的差异
DOI：
10.1111/cas.12180
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Tetsu Akiyama
中科院分区：
文献类型：
--
作者：
Yoshihiro Kawasaki;Shiori Furukawa;Rina Sato;Tetsu Akiyama
肿瘤抑制基因腺瘤性结肠息肉病（APC）在家族性腺瘤性息肉病和许多散发性结直肠肿瘤中发生突变。已知腺瘤性结肠息肉病通过诱导β-连环蛋白降解来负调节Wnt信号传导。大肠腺瘤性息肉病还与鸟嘌呤核苷酸交换因子Asef和Asef 2相互作用并刺激它们的活性，从而调节细胞粘附和迁移。在这里，我们发现在融合的非运动MDCK II细胞中，Asef/Asef 2与APC共定位于顶端和交界处水平的细胞-细胞粘附位点。相反，在含有突变APC的结直肠肿瘤细胞中，大量的Asef/Asef 2和截短的突变APC主要位于细胞质中。这些结果表明，Asef/Asef 2 ‐APC复合物在细胞-细胞接触部位的定位对于调节细胞粘附至关重要，并且这些复合物在结直肠肿瘤细胞中的异常亚细胞定位可能有助于细胞的异常粘附和迁移特性。
The tumor suppressor adenomatous polyposis coli (APC) is mutated in familial adenomatous polyposis and in many sporadic colorectal tumors. Adenomatous polyposis coli is known to negatively regulate Wnt signaling by inducing the degradation of β‐catenin. Adenomatous polyposis coli also interacts with the guanine nucleotide exchange factors Asef and Asef2 and stimulates their activity, thereby regulating cell adhesion and migration. Here we show that in confluent, non‐motile MDCK II cells, Asef/Asef2 are colocalized with APC at the sites of cell–cell adhesion at the apical and junctional levels. In contrast, in colorectal tumor cells containing mutated APC, significant amounts of Asef/Asef2 and the truncated mutant APCs are localized mainly in the cytoplasm. These results suggest that localization of the Asef/Asef2‐APC complex at the sites of cell–cell contact is critical for the regulation of cell adhesion, and that the aberrant subcellular localization of these complexes in colorectal tumor cells may contribute to the cell's aberrant adhesive and migratory properties.