@article{23e344a6682544e7b9fa67805c15f659,
title = "Arid1a Has Context-Dependent Oncogenic and Tumor Suppressor Functions in Liver Cancer",
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. Sun el al. uncover context-specific roles for the SWI/SNF component Arid1a in liver cancer, where elevated Arid1a promotes tumor initiation through CYP450-mediated oxidative stress, whereas reduced Arid1a in established tumors increases metastasis due to reduced expression of inhibitory factors.",
keywords = "ARID1A, SWI/SNF chromatin-remodeling complex, epigenetics, hepatocellular carcinoma, metastasis, mouse models",
author = "Xuxu Sun and Wang, {Sam C.} and Yonglong Wei and Xin Luo and Yuemeng Jia and Lin Li and Purva Gopal and Min Zhu and Ibrahim Nassour and Chuang, {Jen Chieh} and Thomas Maples and Cemre Celen and Nguyen, {Liem H.} and Linwei Wu and Shunjun Fu and Weiping Li and Lijian Hui and Feng Tian and Yuan Ji and Shuyuan Zhang and Mahsa Sorouri and Hwang, {Tae Hyun} and Lynda Letzig and Laura James and Zixi Wang and Yopp, {Adam C.} and Singal, {Amit G.} and Hao Zhu",
note = "Funding Information: We thank J. Shelton and C. Lewis for histology, the UTSW Bioinformatics and the CRI Sequencing Core for sequencing. X.S. was supported by a Hamon Center for Regenerative Science and Medicine award. S.C.W. is a UTSW Disease-Oriented Clinical Scholar, an American College of Surgeon Faculty Research Fellow, and supported by an American Cancer Society Institutional Research grant. X.L. is funded by Cancer Prevention and Research Institute of Texas ( RP150596 ). P.G. was supported by the UTSW Department of Pathology Intramural Research Program. L.N. is an HHMI International Fellow. H.Z. was supported by the Pollack Foundation , a NIH /NIDDK R01 grant ( R01DK111588 ), a Burroughs Wellcome Career Medical award, a CPRIT New Investigator grant ( R1209 ), a CPRIT Early Translation grant ( DP150077 ), a DOD Team Science award ( CA150245 ), and a SUC/ AACR Innovative Research grant ( IRG-10-16 ). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = nov,
day = "13",
doi = "10.1016/j.ccell.2017.10.007",
language = "English (US)",
volume = "32",
pages = "574--589.e6",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}