N-Acetyltransferase 10 Promotes Micronuclei Formation to Activate the Senescence-Associated Secretory Phenotype Machinery in Colorectal Cancer Cells
N-Acetyltransferase 10 Promotes Micronuclei Formation to Activate the Senescence-Associated Secretory Phenotype Machinery in Colorectal Cancer Cells
复制标题
N-乙酰转移酶 10 促进微核形成，激活结直肠癌细胞中衰老相关的分泌表型机制
DOI：
10.1016/j.tranon.2020.100783
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发表时间：
2020-08-01
影响因子：
5
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
Cao, Yanan;Yao, Mengfei;Zhang, Bo
微核（MN）的形成在人类癌细胞中普遍存在，其在激活衰老相关分泌表型（SASP）机制中的作用最近已被确定。然而，MN在调节SASP信号传导中的作用在实际癌症中仍需明确。在此，我们报道在结直肠癌细胞中，NAT10（N - 乙酰转移酶10）的表达可通过DNA复制介导MN形成，并且NAT10阳性的MN可通过与cGAS结合激活SASP。通过Remodelin对NAT10进行化学抑制或基因缺失可显著减少结直肠癌细胞中MN的形成、SASP的激活以及衰老。诸如氧化或缺氧等细胞应激可上调NAT10及其相关的MN形成、衰老以及SASP因子的表达。对临床标本的统计分析揭示了NAT10表达、MN形成、SASP信号传导与结直肠癌临床病理特征之间的相关性。我们的数据表明，NAT10增加MN形成和SASP途径激活，促进结直肠癌进展。
The formation of micronuclei (MN) is prevalent in human cancer cells and its role in activating the senescenceassociated secretory phenotype (SASP) machinery has been identified recently. However, the role of MN in regulation of SASP signaling still needs to define in practical cancers. Here, we reported that in colorectal cancer cells the expression of NAT10 (N-acetyltransferase 10) could mediate MN formation through DNA replication and NAT10-positive MN could activate SASP by binding to cGAS. The chemical inhibition of NAT10 by Remodelin or genomic depletion could markedly reduce MN formation, SASP activation, and senescence in colorectal cancer cells. Cell stress such as oxidative or hypoxia could upregulate NAT10 and its associated MN formation senescence and expression of SASP factors. Statistical analysis of clinical specimens revealed correlations between NAT10 expression, MN formation, SASP signaling, and the clinicopathological features of colorectal cancer. Our data suggest that NAT10 increasing MN formation and SASP pathway activation, promoting colorectal cancer progression.