دورية أكاديمية

DRR regulates AKT activation to drive brain cancer invasion.

التفاصيل البيبلوغرافية
العنوان: DRR regulates AKT activation to drive brain cancer invasion.
المؤلفون: Dudley, A, Sater, M, Le, P U, Trinh, G, Sadr, M S, Bergeron, J, Deleavey, G F, Bedell, B, Damha, M J, Petrecca, K
المصدر: Oncogene; 10/9/2014, Vol. 33 Issue 41, p4952-4960, 9p
مصطلحات موضوعية: GLIOBLASTOMA multiforme treatment, PROTEIN kinase B regulation, CANCER invasiveness, BRAIN cancer, ENZYME activation, GENE expression, FOCAL adhesions
مستخلص: 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. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:09509232
DOI:10.1038/onc.2013.436