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FRK suppresses the proliferation of human glioma cells by inhibiting cyclin D1 nuclear accumulation

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Abstract

The Fyn related kinase (FRK) is a noteworthy member of the Src non-receptor tyrosine kinase family for its distinctive tumor suppressive function. Recently, we have shown that FRK plays a protective role against the progression of glioma by suppressing cell migration and invasion. However, it is unclear whether the cell growth of glioma is also regulated by FRK and by which mechanism FRK alters its specific biological functions. In the current study, we found that FRK over-expression significantly suppressed the proliferation of glioma cells. In contrast, FRK knockdown by siRNA promoted glioma cell growth. In addition, FRK over-expression caused G1 phase arrest as well as apoptosis of glioma cells. Further investigation disclosed that FRK-induced G1 arrest was accompanied by down-regulation of hyperphosphorylated retinoblastoma protein (pRb), which led to the consequent suppression of E2F1. More importantly, we found that over-expression of FRK inhibited proper cyclin D1 accumulation in the nucleus of proliferating cells. Taken together, our results demonstrate a combined mechanism for the anti-proliferative effects of FRK by inhibiting cyclin D1 nucleus accumulation and pRb phosphorylation in glioma cells.

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Abbreviations

FRK:

The Fyn related kinase

pRb:

Retinoblastoma protein

GBM:

Glioblastoma

CDKs:

Cyclin-dependent kinases

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Acknowledgments

The project was supported by National Natural Science Foundation of China (No. 81272777, No. 81302175, No. 81372699); Natural Science Foundation of Jiangsu Province (No. BK2011195); Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 13KJB320025).

Conflict of interest

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, People’s Republic of China

    Lei Hua, Qiong Shi, Wenjian Zhan, Lei Wang, Qingming Meng, Xiuping Zhou & Rutong Yu

  2. Institute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, People’s Republic of China

    Lei Hua, Qiong Shi, Wenjian Zhan, Lei Wang, Qingming Meng, Xiuping Zhou & Rutong Yu

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

    Ming Zhu, Xu Song, Jun Wang, Zhen Fang & Chunting Zhang

  4. Lab of Neurosurgery, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Xiuping Zhou

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  1. Lei Hua
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Correspondence to Xiuping Zhou or Rutong Yu.

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Lei Hua and Ming Zhu have contributed equally to this work.

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Hua, L., Zhu, M., Song, X. et al. FRK suppresses the proliferation of human glioma cells by inhibiting cyclin D1 nuclear accumulation. J Neurooncol 119, 49–58 (2014). https://doi.org/10.1007/s11060-014-1461-y

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  • DOI: https://doi.org/10.1007/s11060-014-1461-y

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