Nature communications · 2026
ARID1A loss drives gastric signet ring cell carcinoma by regulating mucin production and secretion.
СтатьяНазвание и аннотация: Перевод в очереди
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Liu Hongyu, Zhong Ailing, Lu Zhenghao, Gao Limin, Zhang Mengsha, Li Jiaxin, Wang Yingjie, Wang Yiyun, Zhang Lanxin, Zhang Jiabo, Pan Xiangyu, Chen Xuelan, Chen Jingyao, He Siyu, Wang Xinyuan, Wan Xudong, Deng Xintong, Peng Tingfa, Wang Jian, Du Jiajia, Yang Kun, Liu Kai, Chen Xinzu, Chen Xiaolong, Feng Zhe, Wu Baohong, Xu Jing, Zhao Linyong, Zhang Weihan, Yang Shengyong, Wang Yuan, Chen Lu, Xue Zhihong, Zhao Chengjian, Dai Lunzhi, Na Feifei, Hu Jiankun, Liu Yu, Chen Chong
Аннотация
Signet ring cell carcinoma (SRCC) is a lethal malignancy with distinct histologic features, characterized by accumulated mucins in the cytoplasm which compress nuclei. Gastric SRCC is the most common SRCC whose incidence is increasing in recent years. The molecular mechanisms underlying the histopathology remain poorly understood. Here, we report that AT-rich interactive domain-containing protein 1 A (ARID1A), one of the most frequently mutated genes in gastric SRCC, functions as a bona fide tumor suppressor. Its loss, together with Trp53 and Pten loss, drives SRCC in mice. Mechanistically, Arid1a loss upregulates the expressions of mucins through the competing BRD9-containing ncBAF complex. And mucin secretion is impaired by the downregulation of Scin, a direct target of Arid1a in SRCC. Inhibition of Brd9 ameliorates the malignancy of SRCC. Thus, our study reveals dual roles of ARID1A in both mucin production and secretion, providing new mechanistic insights and potential therapeutic vulnerabilities in SRCC.