Journal of Neuro-Oncology

, Volume 110, Issue 1, pp 9–19 | Cite as

FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling

  • Xiuping Zhou
  • Lei Hua
  • Weijian Zhang
  • Ming Zhu
  • Qiong Shi
  • Feng Li
  • Liexiang Zhang
  • Chao Song
  • Rutong YuEmail author
Laboratory Investigation


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.


FRK Migration Invasion Glioma JNK 



The Fyn related kinase


c-Jun NH2-terminal kinase


Matrix metalloproteases



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.


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Xiuping Zhou
    • 1
    • 2
    • 3
  • Lei Hua
    • 1
    • 4
  • Weijian Zhang
    • 4
  • Ming Zhu
    • 4
  • Qiong Shi
    • 1
    • 2
    • 3
  • Feng Li
    • 4
  • Liexiang Zhang
    • 4
  • Chao Song
    • 4
  • Rutong Yu
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of NeurosurgeryAffiliated Hospital of Xuzhou Medical CollegeXuzhouChina
  2. 2.Lab of NeurosurgeryXuzhou Medical CollegeXuzhouChina
  3. 3.Key Laboratory of Brain Disease BiologyAffiliated Hospital of Xuzhou Medical CollegeJiangsuChina
  4. 4.The Graduate SchoolXuzhou Medical CollegeXuzhouChina

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