p53 in the Myeloid Lineage Modulates an Inflammatory Microenvironment Limiting Initiation and Invasion of Intestinal Tumors
Xue-Yan He,
Cong Xiang,
Chen-Xi Zhang,
Yin-Yin Xie,
Lai Chen,
Guo-Xin Zhang,
Yi Lu,
Geng Liu
Affiliations
Xue-Yan He
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Cong Xiang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Chen-Xi Zhang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Yin-Yin Xie
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Lai Chen
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Guo-Xin Zhang
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Yi Lu
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Geng Liu
State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, 12 Xuefu Road, Pukou High-Tec District, Nanjing, JiangSu Province 210061, China
Chronic inflammation promotes the development and progression of various epithelial tumors. Wild-type p53 suppresses inflammation, but it is unclear whether the role of p53 in suppression of inflammation is linked to its tumor suppression function. Here, we established mouse models of myeloid lineage-specific p53 deletion or activation to examine its role in inflammation-related intestinal tumorigenesis. Impaired p53 in the myeloid linage resulted in elevated levels of inflammatory mediators and stimulated adenoma initiation in ApcMin/+ mice. In contrast, mice with mild p53 activation in the myeloid lineage attenuated the inflammatory response and were more resistant to intestinal tumor development and invasion, which were initiated through ApcMin/+ mutation or carcinogen and promoted by colitis. Furthermore, p53 activation also suppressed alternative (M2) macrophage polarization together with c-MYC downregulation. Therefore, as a regulator of macrophage function, p53 is critical to protection against tumorigenesis in a non-cell-autonomous manner.
