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- W2333078063 abstract "Glioblastomas (GBM), the most common primary malignant brain tumors, are highly proliferative and diffusely invasive, and are incurable with current therapies. Genetic and molecular analyses reveal that GBMs frequently harbor mutations that activate the EGFR receptor tyrosine kinase (EGFR) and Pi-3 kinase (PI3K) signaling pathway, and the ability of these mutations to drive gliomagenesis has been verified in mouse models. Yet, current data indicate that EGFR and PI3K signaling cooperates with as yet unknown factors to drive invasive pathology and therapeutic resistance in GBM. To uncover such factors, we used a multidisciplinary approach and performed as series of genetic screen in both Drosophila melanogaster and mammalian GBM model systems, and sought to isolate novel genes that augment EGFR- and PI3K- dependent neoplasia. Results in Drosophila and GBM cell culture systems indicate that Stk17A, a cytoplasmic serine-threonine kinase, is required for GBM invasion and cell proliferation, and that Stk17A loss sensitizes GBM cells to chemotherapy. In GBMs and in lower grade gliomas, Stk17A is subject to copy-gain and/or amplification and becomes overexpressed, and Stk17A overexpression is significantly associated with poor prognosis in patients. Stk17A copy-gain and overexpression are also significantly associated with mutation of EGFR and PI3K pathway components. Our Drosophila data show that overexpression activates Stk17A signaling, which cooperates with oncogenic EGFR mutations to stimulate increased glial cell proliferation and invasion. Our Drosophila data also suggest that Stk17A function is not required for normal glial development. Together, these data indicate that Stk17A drives gliomagenesis, and that Stk17A may serve as a tumor-cell specific therapeutic target for GBM and other gliomas. Therefore, we are examining the molecular function of Stk17A in GBM in order to determine how Stk17A contributes to tumor pathology." @default.
- W2333078063 created "2016-06-24" @default.
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- W2333078063 date "2014-11-01" @default.
- W2333078063 modified "2023-09-23" @default.
- W2333078063 title "CS-29 * A KINOME-WIDE RNAi-SCREEN IN DROSOPHILA GLIA AND HUMAN GBM CELLS REVEALS THAT Stk17A DRIVES NEOPLASTIC GLIAL CELL PROLIFERATION AND INVASION" @default.
- W2333078063 doi "https://doi.org/10.1093/neuonc/nou242.29" @default.
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