Open AccesscGAS restricts colon cancer development by protecting intestinal barrier integrity
Author(s) -
Shuiqing Hu,
Fang Yan,
Xiang Chen,
Tianlei Cheng,
Mingqiu Zhao,
Mingjian Du,
Tuo Li,
Minghao Li,
Zhiqun Zeng,
Yonglong Wei,
Zhimin Gu,
Conggang Zhang,
Lijun Sun,
Zhijian J. Chen
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2105747118
Subject(s) - colorectal cancer , guanosine , cancer research , sting , interferon , biology , colitis , cyclic guanosine monophosphate , intestinal epithelium , cancer , microbiology and biotechnology , immunology , epithelium , biochemistry , endocrinology , genetics , nitric oxide , engineering , aerospace engineering
Significance Intestinal barrier plays a key role in maintaining organismal health. Here we find cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) deficiency compromises intestinal epithelial barrier and exacerbates inflammation. cGAS-deficient mice were highly susceptible to colitis-associated colon cancer (CAC) but not sporadic colon cancer. Surprisingly, the role of cGAS in this process appears to be independent of stimulator of interferon genes (STING)-induced type I interferon signaling, because mice lacking STING or type I interferon receptor were less susceptible to CAC than those lacking cGAS. cGAS but not STING is highly expressed in intestinal stem cells. These results suggest that cGAS has a unique role in protecting the intestinal epithelial barrier and preventing colon cancer development.