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

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Abstract

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.

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Abbreviations

FRK:

The Fyn related kinase

JNK:

c-Jun NH2-terminal kinase

MMPs:

Matrix metalloproteases

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Acknowledgments

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).

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The authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, China

    Xiuping Zhou, Lei Hua, Qiong Shi & Rutong Yu

  2. Lab of Neurosurgery, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Xiuping Zhou, Qiong Shi & Rutong Yu

  3. Key Laboratory of Brain Disease Biology, Affiliated Hospital of Xuzhou Medical College, Jiangsu, China

    Xiuping Zhou, Qiong Shi & Rutong Yu

  4. The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Lei Hua, Weijian Zhang, Ming Zhu, Feng Li, Liexiang Zhang & Chao Song

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  1. Xiuping Zhou
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  2. Lei Hua
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  4. Ming Zhu
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  9. Rutong Yu
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Correspondence to Rutong Yu.

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Xiuping Zhou and Lei Hua contributed equally to this work.

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Zhou, X., Hua, L., Zhang, W. et al. FRK controls migration and invasion of human glioma cells by regulating JNK/c-Jun signaling. J Neurooncol 110, 9–19 (2012). https://doi.org/10.1007/s11060-012-0933-1

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  • DOI: https://doi.org/10.1007/s11060-012-0933-1

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