Augmented -GlcNAcylation alleviates inflammation-mediated colon carcinogenesis via suppression of acute inflammation.

Colon cancer prevalence is high worldwide. -GlcNAcylation has been associated with tumor growth in various tissues, including the colon; however, its link to carcinogenesis is not fully understood. We investigated the association of -GlcNAcylation with colon carcinogenesis using a 1,2-dimethylhydrazine/dextran sodium sulfate-induced colon carcinogenesis model in wild type and -GlcNAc transferase-transgenic (-Tg) mice. The incidence of colon cancer was significantly lower in -Tg than in wild type mice. The colonic length was not shortened in -Tg mice, and NF-κB p65 phosphorylation was strongly suppressed, indicating that reduction of inflammation might be related to the alleviation of colon carcinogenesis. Dextran sodium sulfate-induced acute colitis mice were used to evaluate the effect of -GlcNAcylation on inflammation at the maximal inflammation period. In -Tg mice, NF-κB p65 phosphorylation and interleukin-1β mRNA expression were suppressed. Histochemical staining demonstrated shedding of colon epithelial cells in wild type mice a few days after dextran sodium sulfate treatment, whereas they remained essentially intact in -Tg mice. There were no significant differences on histochemical staining in the remaining epithelia between groups. These data suggest that -GlcNAcylation could prevent colon carcinogenesis through reducing acute maximum inflammation, suggesting modulation of -GlcNAcylation as a novel therapeutic option.