FRK Inhibits Migration and Invasion of Human Glioma Cells by Promoting N-cadherin/β-catenin Complex Formation
FRK Inhibits Migration and Invasion of Human Glioma Cells by Promoting N-cadherin/β-catenin Complex Formation
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FRK 通过促进 N-钙粘蛋白/β-连环蛋白复合物形成来抑制人胶质瘤细胞的迁移和侵袭
DOI：
10.1007/s12031-014-0355-y
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Yu, Rutong
中科院分区：
文献类型：
--
作者：
Shi, Qiong;Song, Xu;Yu, Rutong
Fyn 相关激酶 (FRK) 是 Src 相关酪氨酸激酶的成员，最近据报道在多种癌症类型中发挥有效的肿瘤抑制作用。我们前期的研究也表明FRK过表达抑制胶质瘤细胞的迁移和侵袭。然而，FRK对胶质瘤细胞迁移和侵袭（人类恶性胶质瘤的一个特征）的作用机制仍不清楚。在这项研究中，我们发现 FRK 过度表达会增加 N-钙粘蛋白的蛋白水平，但不会增加 E-钙粘蛋白的蛋白水平。同时，FRK 过表达促进 β-连环蛋白易位至质膜，与 N-钙粘蛋白形成复合物，同时降低核部分中的 β-连环蛋白水平。此外，siRNA下调N-cadherin促进胶质瘤U251和U87细胞的迁移和侵袭，并消除FRK对胶质瘤细胞迁移和侵袭的抑制作用。总之，这些结果表明FRK通过促进N-钙粘蛋白/β-连环蛋白复合物的形成来抑制人神经胶质瘤细胞的迁移和侵袭。
Fyn-related kinase (FRK), a member of Src-related tyrosine kinases, is recently reported to function as a potent tumor suppressor in several cancer types. Our previous study has also shown that FRK over-expression inhibited the migration and invasion of glioma cells. However, the mechanism of FRK effect on glioma cell migration and invasion, a feature of human malignant gliomas, is still not clear. In this study, we found that FRK over-expression increased the protein level of N-cadherin, but not E-cadherin. Meanwhile, FRK over-expression promoted beta-catenin translocation to the plasma membrane, where it formed complex with N-cadherin, while decreased beta-catenin level in the nuclear fraction. In addition, down-regulation of N-cadherin by siRNA promoted the migration and invasion of glioma U251 and U87 cells and abolished the inhibitory effect of FRK on glioma cell migration and invasion. In summary, these results indicate that FRK inhibits migration and invasion of human glioma cells by promoting N-cadherin/beta-catenin complex formation.