CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion
CA125/MUC16 interacts with Src family kinases, and over-expression of its C-terminal fragment in human epithelial cancer cells reduces cell-cell adhesion
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DOI：
10.1016/j.ejcb.2013.10.005
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发表时间：
2013-08-01
影响因子：
6.6
通讯作者：
Nakada, Hiroshi
中科院分区：
文献类型：
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作者：
Akita, Kaoru;Tanaka, Minarni;Nakada, Hiroshi
MUC16/CA125 在人类上皮肿瘤中过度表达，包括卵巢癌、乳腺癌和一些其他癌症。本研究的目的是研究细胞表面 MUC16 如何在功能上参与肿瘤进展，特别关注其细胞质尾部的作用。 C 端 MUC16 片段 (MUC16C) 在上皮癌细胞中的强制表达增加了细胞迁移。我们发现 MUC16C 直接与 Src 家族激酶 (SFK) 相互作用。值得注意的是，与模拟转染子相比，MUC16C 转染子中 E-钙粘蛋白和 β-连环蛋白在细胞-细胞接触处的定位更加分散。此外，MUC16C 转染子显示 Ca2+ 依赖性细胞间粘附减少，但用 SFK 抑制剂 PP2 处理细胞可以恢复这种粘附。由于细胞表面 MUC16 也与 E-钙粘蛋白/β-连环蛋白复合物相关，因此 MUC16 的过度表达及其与 SEK 的相互作用可能会增强 SFK 诱导的 E-钙粘蛋白的失调。因此，我们的结果表明细胞表面MUC16在上皮癌细胞的细胞间粘附中发挥作用。 (C) 2013 爱思唯尔有限公司。版权所有。
MUC16/CA125 is over-expressed in human epithelial tumors including ovarian, breast and some other carcinomas. The purpose of this study is to investigate how cell surface MUC16 is functionally involved in tumor progression, with a special focus on the role of its cytoplasmic tail. Forced expression of C-terminal MUC16 fragment (MUC16C) in epithelial cancer cells increased cell migration. We found that MUC16C directly interacted with Src family kinases (SFKs). Notably, localizations of E-cadherin and beta-catenin at the cell-cell contacts were more diffuse in MUC16C transfectants compared with mock transfectants. Furthermore, MUC16C transfectants showed reduced Ca2+-dependent cell-cell adhesion, but the treatment of cells with PP2, a SFKs inhibitor, restored this. Because cell surface MUC16 is also associated with the E-cadherin/beta-catenin complex, the over-expression of MUC16 and its interaction with SEKs may enhance SFKs-induced deregulation of E-cadherin. Thus, our results suggest a role for cell surface MUC16 in cell-cell adhesion of epithelial cancer cells. (C) 2013 Elsevier GmbH. All rights reserved.