Dual role for inositol-requiring enzyme 1 in promoting the development of hepatocellular carcinoma during diet-induced obesity in mice
文献类型：期刊论文
| 作者 | Shan, Bo1; Wu, Ying2,3; Shan, Bo2,3; Dai, Jianli2,3; Chen, Tianwei2,3; Fang, Jing2,3; Xie, Dong2,3; Xia, Zhixiong4; Liu, Jianfeng4; Liu, Jianmiao4 |
| 刊名 | HEPATOLOGY
 |
| 出版日期 | 2018 |
| 卷号 | 68期号:2页码:533-546 |
| ISSN号 | 0270-9139 |
| 关键词 | DNA methylation differential variability algorithm differentially methylated regions |
| DOI | 10.1002/hep.29871 |
| 文献子类 | Article |
| 英文摘要 | Obesity is associated with both endoplasmic reticulum (ER) stress and chronic metabolic inflammation. ER stress activates the unfolded protein response (UPR) and has been implicated in a variety of cancers, including hepatocellular carcinoma (HCC). It is unclear whether individual UPR pathways are mechanistically linked to HCC development, however. Here we report a dual role for inositol-requiring enzyme 1 (IRE1), the ER-localized UPR signal transducer, in obesity-promoted HCC development. We found that genetic ablation of IRE1 in hepatocytes not only markedly reduced the occurrence of diethylnitrosamine (DEN)-induced HCC in liver-specific IRE1 knockout (LKO) mice when fed a normal chow (NC) diet, but also protected against the acceleration of HCC progression during high-fat diet (HFD) feeding. Irrespective of their adiposity states, LKO mice showed decreased hepatocyte proliferation and signal transducer and activator of transcription 3 (STAT3) activation, even in the face of increased hepatic apoptosis. Furthermore, IRE1 abrogation blunted obesity-associated activation of hepatic inhibitor of nuclear factor kappa B kinase subunit beta (IKK)-nuclear factor kappa B (NF-B) pathway, leading to reduced production of the tumor-promoting inflammatory cytokines tumor necrosis factor (TNF) and interleukin 6 (IL-6). Importantly, higher IRE1 expression along with elevated STAT3 phosphorylation was also observed in the tumor tissues from human HCC patients, correlating with their poorer survival rate. Conclusion: IRE1 acts in a feed-forward loop during obesity-induced metabolic inflammation to promote HCC development through STAT3-mediated hepatocyte proliferation. (Hepatology 2018). |
| 学科主题 | Gastroenterology & Hepatology |
| WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; UNFOLDED-PROTEIN-RESPONSE ; KAPPA-B ; ER STRESS ; SENSOR IRE1-ALPHA ; STAT3 ACTIVATION ; LIVER TUMORIGENESIS ; OXIDATIVE STRESS ; ADIPOSE-TISSUE ; MESSENGER-RNA |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000441244400015 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/505]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Touchstone Diabet Ctr, Dallas, TX USA; 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Shanghai, Peoples R China; 4.Huazhong Univ Sci & Technol, Minist Educ, Key Lab Mol Biophys, Cellular Signaling Lab, Wuhan, Hubei, Peoples R China; 5.Wuhan Univ, Hubei Key Lab Cell Homeostasis, Coll Life Sci, Inst Adv Studies, Wuhan, Hubei, Peoples R China; 6.Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA; 7.Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA, |
| 推荐引用方式 GB/T 7714 | Shan, Bo,Wu, Ying,Shan, Bo,et al. Dual role for inositol-requiring enzyme 1 in promoting the development of hepatocellular carcinoma during diet-induced obesity in mice[J]. HEPATOLOGY,2018,68(2):533-546. |
| APA | Shan, Bo.,Wu, Ying.,Shan, Bo.,Dai, Jianli.,Chen, Tianwei.,...&,.(2018).Dual role for inositol-requiring enzyme 1 in promoting the development of hepatocellular carcinoma during diet-induced obesity in mice.HEPATOLOGY,68(2),533-546. |
| MLA | Shan, Bo,et al."Dual role for inositol-requiring enzyme 1 in promoting the development of hepatocellular carcinoma during diet-induced obesity in mice".HEPATOLOGY 68.2(2018):533-546. |
入库方式： OAI收割
来源：上海营养与健康研究所
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