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DRR regulates AKT activation to drive brain cancer invasion

Oncogene volume 33, pages 4952–4960 (2014)Cite this article

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Abstract

Glioblastoma (GBM) is the most common and invasive adult brain cancer. The rapid invasion of cancer cells into the normal brain is a major cause of treatment failure, yet the mechanisms that regulate this process are poorly understood. We have identified a novel mechanism of brain cancer invasion. We show that downregulated in renal cell carcinoma (DRR), which is newly expressed in invasive gliomas, recruits AKT to focal adhesions. This DRR- induced pathological relocalization of AKT bypasses commonly altered upstream signaling events and leads to AKT activation and invasion. We also developed an oligonucleotide therapeutic that reduces DRR expression and prevents glioma invasion in an in vivo preclinical model of the disease. Our findings identify DRR as a novel GBM target and show that oligonucleotides targeting DRR is a novel therapeutic approach for the treatment of DRR-positive GBMs.

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Acknowledgements

This work was supported in part by grants from Industry Canada, Centre of Excellence for Commercialization (KP), Canadian Institutes for Health Research—Proof-of-Principle Grant (KP and MJD) and Canadian Institutes for Health Research—Operating Grant (MJD). AD was supported by a McGill University Faculty of Medicine Scholarship. GT was supported by a McGill University Faculty of Medicine Scholarship. GFD was supported by a Vanier Canada Graduate Scholarship.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada

    A Dudley, M Sater, P U Le, G Trinh, M S Sadr, J Bergeron, B Bedell & K Petrecca

  2. Department of Chemistry, McGill University, Montreal, Quebec, Canada

    G F Deleavey & M J Damha

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  1. A Dudley
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  2. M Sater
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Dudley, A., Sater, M., Le, P. et al. DRR regulates AKT activation to drive brain cancer invasion. Oncogene 33, 4952–4960 (2014). https://doi.org/10.1038/onc.2013.436

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