FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling.
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.
Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, China.
Xiuping
X
Zhou
Lei
L
Hua
Weijian
W
Zhang
Ming
M
Zhu
Qiong
Q
Shi
Feng
F
Li
Liexiang
L
Zhang
Chao
C
Song
Rutong
R
Yu
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D002465:Cell Movement; D005455:Fluorescent Antibody Technique; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection
D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; D048670:MAP Kinase Kinase 4