小柯机器人

上海第十人民医院方兰、王平研究组合作发现脱甲基蛋氨酸限制促进环GMP-AMP合成酶激活和染色质解栓，从而增强抗肿瘤免疫。2023年6月1日，国际知名学术期刊《癌细胞》发表了这一成果。

他们的研究报告了蛋氨酸剥夺通过阻断其甲基化来增强cGAS活性，甲基化是由甲基转移酶SUV39H1催化的。他们进一步表明甲基化以UHRF1依赖的方式增强cGAS的染色质隔离。阻断cGAS甲基化可增强cGAS介导的抗肿瘤免疫并抑制结直肠肿瘤发生。临床上，人类癌症中cGAS甲基化与不良预后相关。因此，他们的研究结果表明，营养应激通过可逆甲基化促进cGAS激活，并提出了靶向cGAS甲基化治疗癌症的潜在治疗策略。

研究人员表示，cGAS是细胞质DNA的主要传感器，激活I型干扰素信号，在抗肿瘤免疫中发挥重要作用。然而，目前尚不清楚cGAS介导的抗肿瘤活性是否受营养状况的影响。

附：英文原文

Title: Methionine restriction promotes cGAS activation and chromatin untethering through demethylation to enhance antitumor immunity

Author: Lan Fang, Yun Hao, Haihong Yu, Xuemei Gu, Qiao Peng, Huimin Zhuo, Yaxu Li, Zhiyuan Liu, Jia Wang, Yunfei Chen, Jiawen Zhang, Hongling Tian, Yaohui Gao, Renyuan Gao, Hongqi Teng, Zezhi Shan, Jiali Zhu, Zhiqiang Li, Yu’e Liu, Yiyi Zhang, Fei Yu, Zhang Lin, Yujun Hao, Xin Ge, Jian Yuan, Hong-Gang Hu, Yanlei Ma, Huan-Long Qin, Ping Wang

Issue&Volume: 2023-06-01

Abstract: Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment.

DOI: 10.1016/j.ccell.2023.05.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00173-3

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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