FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling
- 788 Downloads
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.
KeywordsFRK Migration Invasion Glioma JNK
The Fyn related kinase
c-Jun NH2-terminal kinase
We are deeply indebted to Dr. Shiaw-Yih Lin of the University of Texas M.D. Anderson Cancer Center in USA for the gift of the plasmid encoding FRK gene. This study was supported in part by the projects of National Natural Science Foundation of China (No. 81072072, No. 31070933), and the grant from State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (SKLN-2011A01).
Conflict of interest
The authors have no conflict of interest.
- 26.Forsyth PA, Wong H, Laing TD, Rewcastle NB, Morris DG, Muzik H, Leco KJ, Johnston RN, Brasher PM, Sutherland G, Edwards DR (1999) Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas. Br J Cancer 79:1828–1835PubMedCrossRefGoogle Scholar
- 30.Vallerie SN, Hotamisligil GS (2010) The role of JNK proteins in metabolism. Sci Transl Med 2:60rv65Google Scholar
- 33.Li Z, Xu X, Bai L, Chen W, Lin Y (2011) Epidermal growth factor receptor-mediated tissue transglutaminase overexpression couples acquired tumor necrosis factor-related apoptosis-inducing ligand resistance and migration through c-FLIP and MMP-9 proteins in lung cancer cells. J Biol Chem 286:21164–21172PubMedCrossRefGoogle Scholar