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Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP

Oncogene volume 29, pages 3501–3508 (2010)Cite this article

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Abstract

The migration and invasion inhibitor protein (MIIP, also known as IIp45) was discovered as a negative regulator of cell migration and invasion in glioma. Our previous studies have shown that the MIIP protein was reduced or undetectable in some tissue samples obtained from patients with glioblastoma. The significance of MIIP in gliomagenesis is unknown. In this study, we report that MIIP has an important role in the inhibition of gliomagenesis and attenuation of mitotic transition. Increased MIIP expression levels inhibited colony formation and cell growth of glioma cell lines in vitro, whereas decreased expression by specific small interfering RNA for MIIP resulted in increased cell growth. Expression of MIIP in a glial-specific mouse model blocked glioma development and progression, thus showing that MIIP is an inhibitor of gliomagenesis. Furthermore, we show that MIIP attenuates mitotic transition and results in increased mitotic catastrophe. The biochemical mechanism of MIIP in this process is associated with its regulation of anaphase-promoting complex (APC/C) activity. MIIP interacts directly with Cdc20, and the interaction of MIIP with Cdc20 inhibits APC/C-mediated degradation of cyclin B1. Thus, MIIP attenuates mitotic transition and increases mitotic catastrophe, thereby inhibiting glioma development and progression.

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Acknowledgements

We thank Kanchana Natarajan-Mendes for her contribution to the cell-cycle assays in this study, and Hong Zheng for her technical assistance. We thank Drs Ying Wu, Limei Hu and Paul Chiao for critically reviewing the manuscript and providing valuable comments. We gratefully thank Dr Kate J Newberry at the Department of Scientific Publications of MD Anderson Cancer Center for editing this paper. This study was partially supported by an ARP Grant from the Texas Higher Education Coordinating Board, the Anthony Bullock Brain Tumor Research Fund and NIH grant RO1 CA98503 (to WZ and GNF). We also thank the National Foundation for Cancer Research, the Goldhirsh Foundation, the James S McDonnell Foundation and the Oreffice Foundation for their support. Sarah M Smith (formerly Sarah M Dunlap) was supported by an NIH Pharmacoinformatics Training Fellowship and an American Legion Fellowship.

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Authors and Affiliations

  1. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    P Ji, S M Smith, Y Wang, R Jiang, S W Song, J M Bruner, G N Fuller & W Zhang

  2. Department of Nutritional Sciences, The University of Texas, Austin, TX, USA

    S M Smith

  3. Departments of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, PR China

    Y Wang

  4. Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, PR China

    R Jiang

  5. Cancer Research Laboratory, Beijing Shijitan Hospital, The Capital Medical University, Beijing, PR China

    S W Song

  6. Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, TX, USA

    B Li & H Yu

  7. Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    R Sawaya

  8. Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J Kuang

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  1. P Ji
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Correspondence to W Zhang.

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Ji, P., Smith, S., Wang, Y. et al. Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP. Oncogene 29, 3501–3508 (2010). https://doi.org/10.1038/onc.2010.114

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