國家衛生研究院 NHRI:Item 3990099045/10471
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    題名: NCoR2 mediates death-resistance and mechano-regulation of glioblastoma multiforme
    作者: Kaushik, S;Tsai, KK;Barnes, JM;Phillips, JJ;Weaver, VM
    貢獻者: National Institute of Cancer Research
    摘要: Glioblastoma Multiforme (GBM) is the most common and one of the deadliest CNS tumors in adults with median survival of less than two years. Current therapeutic regimes, which involve surgery followed by radiotherapy and Temozolomide‐based (TMZ) chemotherapy, are largely ineffective, invariably resulting in tumor recurrence. While the mechanisms underlying treatment resistance are not well understood, the GBM microenvironment and the neural stem cells residing within are believed to be the driving force behind GBM aggressiveness. Nuclear co‐repressor protein NCoR2, is highly upregulated in GBM, specifically post TMZ treatment, and is necessary for tumor cell proliferation (Alrfaei et al., Plos One, 2013). NCoR2 is essential for the activity of histone deacetylase protein HDAC3, whose high expression correlates with poor prognosis in glioma (Zhu et al., Brain Res, 2013). Additionally, NCoR2 is regulated by the Notch pathway, which in turn is implicated in cancer stemness (Ulasov et al., Mol Med, 2011). In this study, we investigate the role of NCoR2 in mediating death‐resistance in GBM and the interplay between NCoR2 and Notch leading to the observed stem‐like phenotype. We show that NCoR2 is upregulated more so in the more aggressive mesenchymal GBM, as compared to its proneural counterpart. Moreover, its regulation is highly mechanosensitive, being upregulated in 3D environments as compared to 2D, suggesting a link between NCoR2‐and the tumor microenvironment in GBM aggressiveness. We therefore postulate that NCoR2 protects cancer cells from chemotherapeutic insult by maintaining their stemness possibly via the Notch pathway, as well as regulating their mechano‐phenotype to provide the ideal niche for tumor relapse.
    日期: 2016-12
    關聯: Molecular Biology of the Cell. 2016 Dec;27:Meeting Abstract P1160.
    Link to: http://www.ascb.org/wp-content/uploads/2016/04/2016ASCBMeeting-PosterAbstracts.pdf
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1059-1524&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000396047100163
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