Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.
Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells.
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自噬介导的细胞质中游离基因组 DNA 的清除可保护癌细胞的生长和存活
DOI：
10.3389/fonc.2021.667920
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Yao M;Wu Y;Cao Y;Liu H;Ma N;Chai Y;Zhang S;Zhang H;Nong L;Liang L;Zhang B
近年来，环鸟苷酸-腺苷酸合成酶（cGAS）介导的衰老相关分泌表型（SASP）和DNA诱导的自噬（DNA自噬）已得到广泛研究。然而，cGAS介导的自噬在癌细胞中尚未阐明。所述研究表明，在具有高微核（MN）形成的BT - 549乳腺癌细胞系中可检测到活跃的DNA自噬，但未检测到SASP活性。DNA自噬被确定为细胞质中游离基因组DNA的选择性自噬，而非核自噬。细胞质中的DNA自噬过程可由cGAS启动，并且通常与由SQSTM1介导的泛素化组蛋白的自噬协同作用。细胞质DNA与组蛋白等核蛋白一起，可能源于DNA复制诱导的核损伤和微核崩溃。通过化学抑制剂抑制自噬以及对cGAS或SQSTM1进行基因沉默可抑制癌细胞的生长和存活，并且诱导的DNA损伤可增加对这些抑制剂的敏感性。此外，对其他几种人类癌细胞的进一步观察表明，较高的相对DNA自噬或DNA损伤的增强也可增加这些细胞对DNA自噬抑制的敏感性。
The cGAS (GMP-AMP synthase)-mediated senescence-associated secretory phenotype (SASP) and DNA-induced autophagy (DNA autophagy) have been extensively investigated in recent years. However, cGAS-mediated autophagy has not been elucidated in cancer cells. The described investigation revealed that active DNA autophagy but not SASP activity could be detected in the BT-549 breast cancer cell line with high micronucleus (MN) formation. DNA autophagy was identified as selective autophagy of free genomic DNA in the cytoplasm but not nucleophagy. The process of DNA autophagy in the cytosol could be initiate by cGAS and usually cooperates with SQSTM1-mediated autophagy of ubiquitinated histones. Cytoplasmic DNA, together with nuclear proteins such as histones, could be derived from DNA replication-induced nuclear damage and MN collapse. The inhibition of autophagy through chemical inhibitors as well as the genomic silencing of cGAS or SQSTM1 could suppress the growth and survival of cancer cells, and induced DNA damage could increase the sensitivity to these inhibitors. Furthermore, expanded observations of several other kinds of human cancer cells indicated that high relative DNA autophagy or enhancement of DNA damage could also increase or sensitize these cells to inhibition of DNA autophagy.
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影响因子：
29
作者：
Kimmelman AC;White E
通讯作者：
White E
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
2.2
作者：
Goyal G;Fan T;Silberstein PT
通讯作者：
Silberstein PT
影响因子：
--
作者：
Fernandez-Martinez, Javier;LaCava, John;Rout, Michael P
通讯作者：
Rout, Michael P
Sidt2通过自噬调节肝细胞脂质代谢
影响因子：
6.5
作者：
Chen, Xueru;Gu, Xuefan;Zhang, Huiwen
通讯作者：
Zhang, Huiwen