| Literature DB >> 29136504 |
Xuxu Sun1, Sam C Wang2, Yonglong Wei1, Xin Luo3, Yuemeng Jia1, Lin Li1, Purva Gopal4, Min Zhu1, Ibrahim Nassour2, Jen-Chieh Chuang1, Thomas Maples1, Cemre Celen1, Liem H Nguyen5, Linwei Wu6, Shunjun Fu7, Weiping Li8, Lijian Hui9, Feng Tian10, Yuan Ji10, Shuyuan Zhang1, Mahsa Sorouri1, Tae Hyun Hwang11, Lynda Letzig12, Laura James12, Zixi Wang1, Adam C Yopp13, Amit G Singal14, Hao Zhu15.
Abstract
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be tumor suppressive. In some hepatocellular carcinoma patients, ARID1A was highly expressed in primary tumors but not in metastatic lesions, suggesting that ARID1A can be lost after initiation. Mice with liver-specific homozygous or heterozygous Arid1a loss were resistant to tumor initiation while ARID1A overexpression accelerated initiation. In contrast, homozygous or heterozygous Arid1a loss in established tumors accelerated progression and metastasis. Mechanistically, gain of Arid1a function promoted initiation by increasing CYP450-mediated oxidative stress, while loss of Arid1a within tumors decreased chromatin accessibility and reduced transcription of genes associated with migration, invasion, and metastasis. In summary, ARID1A has context-dependent tumor-suppressive and oncogenic roles in cancer.Entities:
Keywords: ARID1A; SWI/SNF chromatin-remodeling complex; epigenetics; hepatocellular carcinoma; metastasis; mouse models
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Year: 2017 PMID： 29136504 PMCID： PMC5728182 DOI： 10.1016/j.ccell.2017.10.007
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743