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FRK通过促进N-钙黏蛋白/β-连环蛋白复合物的形成来抑制人胶质瘤细胞的迁移和侵袭。

FRK inhibits migration and invasion of human glioma cells by promoting N-cadherin/β-catenin complex formation.

作者信息

Shi Qiong, Song Xu, Wang Jun, Gu Jia, Zhang Weijian, Hu Jinxia, Zhou Xiuping, Yu Rutong

机构信息

Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.

Institute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.

出版信息

J Mol Neurosci. 2015 Jan;55(1):32-41. doi: 10.1007/s12031-014-0355-y. Epub 2014 Jun 27.

Abstract

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 β-catenin translocation to the plasma membrane, where it formed complex with N-cadherin, while decreased β-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/β-catenin complex formation.

摘要

Fyn相关激酶(FRK)是Src相关酪氨酸激酶家族的成员,最近有报道称它在几种癌症类型中作为一种有效的肿瘤抑制因子发挥作用。我们之前的研究也表明,FRK的过表达抑制了胶质瘤细胞的迁移和侵袭。然而,FRK影响胶质瘤细胞迁移和侵袭(人类恶性胶质瘤的一个特征)的机制仍不清楚。在本研究中,我们发现FRK的过表达增加了N-钙黏蛋白的蛋白水平,但E-钙黏蛋白的水平未增加。同时,FRK的过表达促进了β-连环蛋白向质膜的转位,在质膜上它与N-钙黏蛋白形成复合物,而核部分中的β-连环蛋白水平降低。此外,通过小干扰RNA(siRNA)下调N-钙黏蛋白可促进胶质瘤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-钙黏蛋白/β-连环蛋白复合物的形成来抑制人类胶质瘤细胞的迁移和侵袭。

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