中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海营养与健康研究所
  3. 中国科学院上海生命科学研究院营养科学研究所
Knockdown of IRE1 alpha inhibits colonic tumorigenesis through decreasing beta-catenin and IRE1 alpha targeting suppresses colon cancer cells

文献类型：期刊论文

作者Li, X-X1; Zhang, H-S1; Xu, Y-M1; Zhang, R-J1; Chen, Y.1; Fan, L.1; Qin, Y-Q1; Fang, J.1; Liu, Y.2; Li, M.3
刊名ONCOGENE
出版日期2017
卷号36期号:48页码:6738-6746
关键词Cohort studies Meta-analysis Nested case-control study Retinol binding protein 4 Type 2 diabetes
ISSN号0950-9232
DOI10.1038/onc.2017.284
文献子类Article
英文摘要The endoplasmic reticulum (ER) stress occurs frequently in cancers. The unfolded protein response (UPR) is activated to cope with ER stress. This has generated widespread interest in targeting UPR as therapeutic strategies. Inositol-requiring transmembrane kinase/endonuclease 1 alpha (IRE1 alpha), an ER stress sensor, is a key component of UPR. However, the role of IRE1 alpha in tumorigenesis remains unclear. The purpose of this work is to investigate the role of IRE1 alpha in colon cancer and to determine whether IRE1 alpha could serve as a target for therapy. We found that knockdown of IRE1 alpha suppressed the proliferation of colon cancer cells in vitro and xenograft growth in vivo. Inhibition of expression of IRE1 alpha decreased stemness of colon cancer stem cells (CSCs) and attenuated growth of intestinal organoids. Genetic ablation of IRE1 alpha prevented the colitis-associated colonic tumorigenesis in mice. The mechanistic study indicates that knockdown of IRE1 alpha repressed the expression of beta-catenin, a key factor that drives colonic tumorigenesis, through activating pancreatic ER kinase/eukaryotic translation initiation factor 2 alpha signaling. We found that the IRE1a-specific inhibitor 4 mu 8C could suppress the production of beta-catenin, inhibited the proliferation of colon cancer cells, repressed colon CSCs and prevented xenograft growth. The results suggest that IRE1a has a critical role in colonic tumorigenesis and IRE1 alpha targeting might be a strategy for treatment of colon cancers.
学科主题Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS关键词UNFOLDED PROTEIN RESPONSE ; ENDOPLASMIC-RETICULUM STRESS ; TO-MESENCHYMAL TRANSITION ; ER STRESS ; STEM-CELLS ; MULTIPLE-MYELOMA ; EPITHELIAL-CELLS ; BREAST-CANCER ; CYCLIN D1 ; WNT
语种英语
WOS记录号WOS:000416780800008
出版者NATURE PUBLISHING GROUP
版本出版稿
源URL[http://202.127.25.144/handle/331004/1175]  
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 Chinese Acad Sci, Shanghai Inst Biol Sci, Chinese Acad Sci, Key Lab Food Safety Res,Inst Nutrit Sci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China;
2.Wuhan Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China;
3.Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA,
推荐引用方式
GB/T 7714		 Li, X-X,Zhang, H-S,Xu, Y-M,et al. Knockdown of IRE1 alpha inhibits colonic tumorigenesis through decreasing beta-catenin and IRE1 alpha targeting suppresses colon cancer cells[J]. ONCOGENE,2017,36(48):6738-6746.
APA Li, X-X.,Zhang, H-S.,Xu, Y-M.,Zhang, R-J.,Chen, Y..,...&,.(2017).Knockdown of IRE1 alpha inhibits colonic tumorigenesis through decreasing beta-catenin and IRE1 alpha targeting suppresses colon cancer cells.ONCOGENE,36(48),6738-6746.
MLA Li, X-X,et al."Knockdown of IRE1 alpha inhibits colonic tumorigenesis through decreasing beta-catenin and IRE1 alpha targeting suppresses colon cancer cells".ONCOGENE 36.48(2017):6738-6746.

入库方式： OAI收割

来源：上海营养与健康研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。