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Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression

Oncogene volume 36, pages 4562–4572 (2017)Cite this article

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Abstract

Glioblastoma (GBM) is the most common primary brain tumor and has a dismal prognosis. Amplification of chromosome 12q13-q15 (Cyclin-dependent kinase 4 (CDK4) amplicon) is frequently observed in numerous human cancers including GBM. Phosphoinositide 3-kinase enhancer (PIKE) is a group of GTP-binding proteins that belong to the subgroup of centaurin GTPase family, encoded by CENTG1 located in CDK4 amplicon. However, the pathological significance of CDK4 amplicon in GBM formation remains incompletely understood. In the current study, we show that co-expression of PIKE-A and CDK4 in TP53/PTEN double knockout GBM mouse model additively shortens the latency of glioma onset and survival compared to overexpression of these genes alone. Consequently, p-mTOR, p-Akt and p-ERK pathways are highly upregulated in the brain tumors, in alignment with their oncogenic activities by CDK4 and PIKE-A stably transfected in GBM cell lines. Hence, our findings support that PIKE amplification or overexpression coordinately acts with CDK4 to drive GBM tumorigenesis.

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Acknowledgements

This work has been funded in part with Federal funds from National Cancer Institute (NCI), National Institutes of Health (NIH), under the NCI Chemical Biology Consortium Contract HHSN261200800001E (HF; KY), NIH grant RO1 CA186918 (KY), U01 CA168449 (HF), SBTF Foundation (KY), National Natural Science Foundation of China (No.81672781). We are thankful to Dr Suzanne J. Baker for the PTEN/P53 loxP/loxP mice and to the Winship Cancer Institute of Emory University Cancer Center Support Grant P30-CA138292.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Q Qi, S S Kang, S Zhang, D J Brat & K Ye

  2. Department of Pharmacology and Emory Chemical Biology Discovery Center, Emory University School of Medicine,

    Q Qi, C Pham & H Fu

  3. Atlanta, GA, USA

    Q Qi, C Pham & H Fu

  4. Institute of Tumor Pharmacology, Jinan University College of Pharmacy, Guangzhou, China

    S Zhang

  5. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine,

    H Fu

  6. Atlanta, GA, USA

    H Fu

  7. Department of Regenerative Medicine, Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

    K Ye

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  1. Q Qi
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Correspondence to K Ye.

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Qi, Q., Kang, S., Zhang, S. et al. Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression. Oncogene 36, 4562–4572 (2017). https://doi.org/10.1038/onc.2017.67

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  • DOI: https://doi.org/10.1038/onc.2017.67

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