Lgals3bp suppresses colon inflammation and tumorigenesis through the downregulation of TAK1-NF-κB signaling.

Galectin 3-binding protein (LGALS3BP, also known as 90K) is a multifunctional glycoprotein involved in immunity and cancer. However, its precise role in colon inflammation and tumorigenesis remains unclear. Here, we showed that Lgals3bp mice were highly susceptible to colitis and colon tumorigenesis, accompanied by the induction of inflammatory responses. In acute colitis, NF-κB was highly activated in the colon of Lgals3bp mice, leading to the excessive production of pro-inflammatory cytokines, such as IL-6, TNFα, and IL-1β. Mechanistically, Lgals3bp suppressed NF-κB through the downregulation of TAK1 in colon epithelial cells. There was no significant difference in the pro-inflammatory cytokine levels between wild-type and Lgals3bp mice in a chronic inflammatory state, during colon tumorigenesis. Instead, Lgals3bp mice showed elevated levels of GM-CSF, compared to those in WT mice. We also found that GM-CSF promoted the accumulation of myeloid-derived suppressor cells and ultimately increased colon tumorigenesis in Lgals3bp mice. Taken together, Lgals3bp plays a critical role in the suppression of colitis and colon tumorigenesis through the downregulation of the TAK1-NF-κB-cytokine axis. These findings suggest that LGALS3BP is a novel immunotherapeutic target for colon inflammation and tumorigenesis.