FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling
FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling
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DOI：
10.1007/s11060-012-0933-1
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发表时间：
2012-10-01
影响因子：
3.9
通讯作者：
Yu, Rutong
中科院分区：
文献类型：
--
作者：
Zhou, Xiuping;Hua, Lei;Yu, Rutong
Fyn相关激酶(Fyn Related Kinase，Frk)是细胞内Src相关酪氨酸激酶的一员，最近被报道在几种癌症类型中发挥强大的肿瘤抑制作用。然而，由于人恶性胶质瘤具有较高的侵袭和迁移潜能，其在胶质瘤中的表达水平和功能意义尚未见报道。我们在此报道了Frk通过抑制c-Jun氨基末端蛋白激酶(JNK)/c-Jun信号通路来减少胶质瘤细胞的迁移和侵袭。在人脑胶质瘤组织中，Frk的mRNA和蛋白水平均显著下调。此外，Frk的过表达抑制了胶质瘤细胞的迁移和侵袭，并抑制了作为迁移和侵袭指标的基质金属蛋白酶2(MMP2)的分泌。此外，Frk的过表达抑制了JNK和c-Jun的磷酸化，这两个蛋白在细胞的迁移和侵袭中发挥着重要作用。最后，FRK对细胞迁移和侵袭的影响以及对JNK/c-Jun的抑制作用可被JNK的特异性激活剂茴香霉素所阻断。综上所述，这些结果清楚地表明，Frk可能通过抑制细胞的迁移和侵袭而对胶质瘤的进展起到保护作用，提示Frk的详细机制和临床意义有待进一步研究。
The Fyn related kinase (FRK), a member of intracellular Src-related tyrosine kinases, was recently reported to function as a potent tumor suppressor in several cancer types. However, the expression level and functional significance of FRK in human malignant glioma, which is characterized by high migration and invasion potential, have never been investigated. We reported here that FRK reduced cell migration and invasion via inhibiting the c-Jun N-terminal protein kinase (JNK)/c-Jun signaling pathway in glioma cells. The mRNA and protein levels of FRK were significantly down-regulated in human primary glioma tissues. In addition, over-expression of FRK inhibited migration and invasion of glioma cells and excretion of the matrix metalloprotease 2 (MMP2), an index of migration and invasion. Furthermore, over-expression of FRK inhibited phosphorylation of JNK and c-Jun, which play important role in cell migration and invasion. Finally, the effects of FRK on cell migration and invasion and JNK/c-Jun inhibition were abolished by anisomycin, a JNK specific activator. In summary, these results clearly indicate that FRK may play a protective role against the progression of glioma by suppressing cell migration and invasion, suggesting that FRK needs to be further studied in its detail mechanism and clinical significant.