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      AKT/GSK3β Signaling in Glioblastoma

      research-article
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      Neurochemical Research
      Springer US
      Glioblastoma, AKT, GSK3β, Therapeutic target

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          Abstract

          Glioblastoma (GBM) is the most aggressive of primary brain tumors. Despite the progress in understanding the biology of the pathogenesis of glioma made during the past decade, the clinical outcome of patients with GBM remains still poor. Deregulation of many signaling pathways involved in growth, survival, migration and resistance to treatment has been implicated in pathogenesis of GBM. One of these pathways is phosphatidylinositol-3 kinases (PI3K)/protein kinase B (AKT)/rapamycin-sensitive mTOR-complex (mTOR) pathway, intensively studied and widely described so far. Much less attention has been paid to the role of glycogen synthase kinase 3 β (GSK3β), a target of AKT. In this review we focus on the function of AKT/GSK3β signaling in GBM.

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          Most cited references53

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          Identification of c-MYC as a target of the APC pathway.

          The adenomatous polyposis coli gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of beta-catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers.
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            The glamour and gloom of glycogen synthase kinase-3.

            Glycogen synthase kinase-3 (GSK3) is now recognized as a key component of a surprisingly large number of cellular processes and diseases. Several mechanisms play a part in controlling the actions of GSK3, including phosphorylation, protein complex formation, and subcellular distribution. These are used to control and direct the far-reaching influences of GSK3 on cellular structure, growth, motility and apoptosis. Dysregulation of GSK3 is linked to several prevalent pathological conditions, such as diabetes and/or insulin resistance, and Alzheimer's disease. Therefore, much effort is currently directed towards understanding the functions and control of GSK3, and identifying methods capable of diminishing the deleterious impact of GSK3 in pathological conditions.
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              Is Open Access

              PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma

              Glioblastoma multiform (GBM) is the most common malignant glioma of all the brain tumors and currently effective treatment options are still lacking. GBM is frequently accompanied with overexpression and/or mutation of epidermal growth factor receptor (EGFR), which subsequently leads to activation of many downstream signal pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt/rapamycin-sensitive mTOR-complex (mTOR) pathway. Here we explored the reason why inhibition of the pathway may serve as a compelling therapeutic target for the disease, and provided an update data of EFGR and PI3K/Akt/mTOR inhibitors in clinical trials.
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                Author and article information

                Contributors
                +48 22 6086416 , mszeliga@imdik.pan.pl
                Journal
                Neurochem Res
                Neurochem. Res
                Neurochemical Research
                Springer US (New York )
                0364-3190
                1573-6903
                27 August 2016
                27 August 2016
                2017
                : 42
                : 3
                : 918-924
                Affiliations
                ISNI 0000 0001 1958 0162, GRID grid.413454.3, Department of Neurotoxicology, Mossakowski Medical Research Centre, , Polish Academy of Sciences, ; 5 Pawińskiego Str., 02-106 Warsaw, Poland
                Article
                2044
                10.1007/s11064-016-2044-4
                5357492
                27568206
                bb4746dc-2c91-4f1f-bfd8-c0cc7adfacfb
                © The Author(s) 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 2 June 2016
                : 28 July 2016
                : 23 August 2016
                Funding
                Funded by: National Scientific Leading Centre
                Award ID: KNOW-MMRC
                Award Recipient :
                Categories
                Original Paper
                Custom metadata
                © Springer Science+Business Media New York 2017

                Neurosciences
                glioblastoma,akt,gsk3β,therapeutic target
                Neurosciences
                glioblastoma, akt, gsk3β, therapeutic target

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