细胞生物学
癌症研究
细胞周期
核糖核酸
先天免疫系统
细胞
作者
Jie Chen,Shane M. Harding,Ramakrishnan Natesan,Lei Tian,Joseph L. Benci,Weihua Li,Andy J. Minn,Irfan A. Asangani,Roger A. Greenberg
出处
期刊:Cell Reports
[Elsevier]
日期:2020-09-01
卷期号:32 (9): 108080-
被引量:24
标识
DOI:10.1016/j.celrep.2020.108080
摘要
The DNA-dependent pattern recognition receptor, cGAS (cyclic GMP-AMP synthase), mediates communication between the DNA damage and the immune responses. Mitotic chromosome missegregation stimulates cGAS activity; however, it is unclear whether progression through mitosis is required for cancercell-intrinsic activation of anti-tumor immune responses. Moreover, it is unknown whether cell cycle checkpoint disruption can restore responses in cancer cells that are recalcitrant to DNAdamage-induced inflammation. Here, we demonstrate that prolonged cell cycle arrest at the G2-mitosis boundary from either excessive DNA damage or CDK1 inhibition prevents inflammatory-stimulated gene expression and immune-mediated destruction of distal tumors. Remarkably, DNAdamage-induced inflammatory signaling is restored in a RIG-I-dependent manner upon concomitant disruption of p53 and the G2 checkpoint. These findings link aberrant cell progression and p53 loss to an expanded spectrum of damage-associated molecular pattern recognition and have implications for the design of rational approaches to augment anti-tumor immune responses.
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