| First Author | Wang H | Year | 2021 |
| Journal | Carcinogenesis | Volume | 42 |
| Issue | 4 | Pages | 557-569 |
| PubMed ID | 33196831 | Mgi Jnum | J:305686 |
| Mgi Id | MGI:6706850 | Doi | 10.1093/carcin/bgaa122 |
| Citation | Wang H, et al. (2021) Colitis-induced IL11 promotes colon carcinogenesis. Carcinogenesis 42(4):557-569 |
| abstractText | Colitis increases the risk of colorectal cancer; however, the mechanism of the association between colitis and cancer remains largely unknown. To identify colitis-associated cancer promoting factors, we investigated gene expression changes caused by dextran sulfate sodium (DSS)-induced colitis in mice. By analyzing gene expression profiles, we found that IL11 was upregulated in DSS-induced colitis tissue and 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP)/DSS-induced colon tumours in mice as well as in human colorectal cancer. By characterizing the activation/phosphorylation of STAT3 (pSTAT3), we found that pSTAT3 was induced transiently in colitis, but maintained at higher levels from hyper-proliferative dysplastic lesions to tumours. Using the IL11 receptor (IL11Ralpha1) knockout mice, we found that pSTAT3 in the newly regenerated crypt epithelial cells in colitis is abolished in IL11Ralpha1+/- and -/- mice, suggesting that colitis-induced IL11 activates STAT3 in colon crypt epithelial cells. Moreover, colitis-promoted colon carcinogenesis was significantly reduced in IL11Ralpha1+/- and -/- mice. To determine the roles of the IL11 in colitis, we found that the inhibition of IL11 signalling by recombinant IL11 antagonist mutein during colitis was sufficient to attenuate colitis-promoted carcinogenesis. Together, our results demonstrated that colitis-induced IL11 plays critical roles in creating cancer promoting microenvironment to facilitate the development of colon cancer from dormant premalignant cells. |
