國家衛生研究院 NHRI:Item 3990099045/13377
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    題名: Arginine is an epigenetic regulator targeting TEAD4 to modulate OXPHOS in prostate cancer cells
    作者: Chen, CL;Hsu, SC;Chung, TY;Chu, CY;Wang, HJ;Hsiao, PW;Yeh, SD;Ann, DK;Yen, Y;Kung, HJ
    貢獻者: Institute of Molecular and Genomic Medicine;Institute of Cellular and Systems Medicine
    摘要: Arginine plays diverse roles in cellular physiology. As a semi-essential amino acid, arginine deprivation has been used to target cancers with arginine synthesis deficiency. Arginine-deprived cancer cells exhibit mitochondrial dysfunction, transcriptional reprogramming and eventual cell death. In this study, we show in prostate cancer cells that arginine acts as an epigenetic regulator to modulate histone acetylation, leading to global upregulation of nuclear-encoded oxidative phosphorylation (OXPHOS) genes. TEAD4 is retained in the nucleus by arginine, enhancing its recruitment to the promoter/enhancer regions of OXPHOS genes and mediating coordinated upregulation in a YAP1-independent but mTOR-dependent manner. Arginine also activates the expression of lysine acetyl-transferases and increases overall levels of acetylated histones and acetyl-CoA, facilitating TEAD4 recruitment. Silencing of TEAD4 suppresses OXPHOS functions and prostate cancer cell growth in vitro and in vivo. Given the strong correlation of TEAD4 expression and prostate carcinogenesis, targeting TEAD4 may be beneficially used to enhance arginine-deprivation therapy and prostate cancer therapy.
    日期: 2021-04-23
    關聯: Nature Communications. 2021 Apr 23;12:Article number 2398.
    Link to: http://dx.doi.org/10.1038/s41467-021-22652-9
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000656461300002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85104839436
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