國家衛生研究院 NHRI:Item 3990099045/14263
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    題名: Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity
    作者: Tsai, KK;Huang, SS;Northey, JJ;Liao, WY;Hsu, CC;Cheng, LH;Werner, ME;Chuu, CP;Chatterjee, C;Lakins, JN;Weaver, VM
    貢獻者: Institute of Cellular and Systems Medicine
    摘要: Resistance to antitumor treatment contributes to patient mortality. Functional proteomic screening of organoids derived from chemotherapy-treated patients with breast cancer identified nuclear receptor corepressor 2 (NCOR2) histone deacetylase as an inhibitor of cytotoxic stress response and antitumor immunity. High NCOR2 in the tumors of patients with breast cancer predicted chemotherapy refractoriness, tumor recurrence and poor prognosis. Molecular studies revealed that NCOR2 inhibits antitumor treatment by regulating histone deacetylase 3 (HDAC3) to repress interferon regulatory factor 1 (IRF-1)-dependent gene expression and interferon (IFN) signaling. Reducing NCOR2 or impeding its epigenetic activity by modifying its interaction with HDAC3 enhanced chemotherapy responsiveness and restored antitumor immunity. An adeno-associated viral NCOR2–HDAC3 competitor potentiated chemotherapy and immune checkpoint therapy in culture and in vivo by permitting transcription of IRF-1-regulated proapoptosis and inflammatory genes to increase IFN-γ signaling. The findings illustrate the utility of patient-derived organoids for drug discovery and suggest that targeting stress and inflammatory–repressor complexes such as NCOR2–HDAC3 could overcome treatment resistance and improve the outcome of patients with cancer.
    日期: 2022-05-26
    關聯: Nature Cancer. 2022 May 26;3:734-752.
    Link to: http://dx.doi.org/10.1038/s43018-022-00375-0
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2662-1347&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000805499000001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85130687862
    顯示於類別:[褚志斌] 期刊論文

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