机构：[1]Department of Pathology, Medical College of Soochow University, Soochow University, Suzhou 215123, People’s Republic of China,[2]Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China,[3]Department of Pathology, Huizhou Health Sciences Polytechnic, Huizhou 516000, People’s Republic of China,[4]Department of Basic Medicine,School of Medicine, Hubei Three Gorges Polytechnic, Yichang 443000, People’s Republic of China,[5]Department of Pathology, Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, People’s Republic of China,[6]Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People’s Republic of China
Previously we reported that ErbB4 played a protective role in chronic liver injury and hepatocellular carcinoma. Herein, we examined the role of ErbB4 in the development of colitis-associated cancer (CAC) in ErbB4 knockout mice models, in vitro cell lines and clinical samples. We found that ErbB4 deficiency may lead to more severe inflammation, slower recovery, and the development of CAC. Further, loss of ErbB4 could activate KRAS by up regulating rate-limiting enzymes in cholesterol metabolism pathway through interacting with the transcription factor SREBF1. In clinic samples, ErbB4 is down-regulated in colonic tissues from Crohn's disease patients. And data from The Cancer Genome Atlas also showed significant negative correlation between ErbB4 and several cholesterol metabolic enzymes. In conclusion, our study uncovers ErbB4 as a protector in the development of colitis-associated cancer, for its loss could activate KRAS by up regulating cholesterol metabolism through interaction with SREBF1.
基金：
The National Natural Science Foundation of China (Grant
31471189), the National Science Fund for Distinguished Young
Scholars (Grant 81525020), the National Key R&D Program of China
(2017YFC1309000), the Natural Science Foundation of Jiangsu
Province (BE2016666), the Postdoctoral Scientific Research Aid
Program of China (Grant 2016M590501), the Postdoctoral Scientific
Research Aid Program of Jiangsu Province (Grant 1501065A),
and the Postgraduate Research and Practice Innovation Program
of Jiangsu Province (Grant KYCX17_2032).
第一作者机构：[1]Department of Pathology, Medical College of Soochow University, Soochow University, Suzhou 215123, People’s Republic of China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pathology, Medical College of Soochow University, Soochow University, Suzhou 215123, People’s Republic of China,[2]Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China,[5]Department of Pathology, Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, People’s Republic of China,
推荐引用方式(GB/T 7714)：
Hengli Ni,Lin Chen,Liming Song,et al.ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism.[J].Carcinogenesis.2018,doi:10.1093/carcin/bgy164.
APA：
Hengli Ni,Lin Chen,Liming Song,Lina Sun,Hongxia Cui...&Jianming Li.(2018).ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism..Carcinogenesis,,
MLA：
Hengli Ni,et al."ErbB4 acts as a suppressor in colitis and its associated carcinoma by negatively regulating cholesterol metabolism.".Carcinogenesis .(2018)
