國家衛生研究院 NHRI:Item 3990099045/13535
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    題名: Ionizing radiation induces resistant glioblastoma stem-like cells by promoting autophagy via the Wnt/beta-Catenin pathway
    其他題名: Ionizing radiation induces resistant glioblastoma stem-like cells by promoting autophagy via the Wnt/β-Catenin pathway
    作者: Tsai, CY;Ko, HJ;Huang, CYF;Lin, CY;Chiou, SJ;Su, YF;Lieu, AS;Loh, JK;Kwan, AL;Chuang, TH;Hong, YR
    貢獻者: NHRI Graduate Student Program;Immunology Research Center
    摘要: Therapeutic resistance in recurrent glioblastoma multiforme (GBM) after concurrent chemoradiotherapy (CCRT) is a challenging issue. Although standard fractionated radiation is essential to treat GBM, it has led to local recurrence along with therapy-resistant cells in the ionizing radiation (IR) field. Lines of evidence showed cancer stem cells (CSCs) play a vital role in therapy resistance in many cancer types, including GBM. However, the molecular mechanism is poorly understood. Here, we proposed that autophagy could be involved in GSC induction for radioresistance. In a clinical setting, patients who received radiation/chemotherapy had higher LC3II expression and showed poor overall survival compared with those with low LC3 II. In a cell model, U87MG and GBM8401 expressed high level of stemness markers CD133, CD44, Nestin, and autophagy marker P62/LC3II after receiving standard fractionated IR. Furthermore, Wnt/beta-catenin proved to be a potential pathway and related to P62 by using proteasome inhibitor (MG132). Moreover, pharmacological inhibition of autophagy with BAF and CQ inhibit GSC cell growth by impairing autophagy flux as demonstrated by decrease Nestin, CD133, and SOX-2 levels. In conclusion, we demonstrated that fractionated IR could induce GSCs with the stemness phenotype by P62-mediated autophagy through the Wnt/beta-catenin for radioresistance. This study offers a new therapeutic strategy for targeting GBM in the future.
    日期: 2021-05-18
    關聯: Life-Basel. 2021 May 18;11(5):Article number 451.
    Link to: http://dx.doi.org/10.3390/life11050451
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2075-1729&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000654119600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85106870718
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