Role of the β-Catenin/REG Iα Axis in the Proliferation of Sessile Serrated Adenoma/Polyps Associated with Fusobacterium nucleatum

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma-carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the beta-catenin/REG I alpha axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of beta-catenin, REG I alpha and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed beta-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of beta-catenin (87.5%) and higher REG I alpha scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing beta-catenin in nuclei had significantly higher REG I alpha scores and Ki67 labeling indices than those expressing beta-catenin on cytomembranes. The REG I alpha score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear beta-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of beta-catenin nuclear translocation and REG I alpha expression.

Automated summary

The study suggests that Fusobacterium nucleatum may play a role in the proliferation of sessile serrated adenoma/polyps (SSA/Ps) by promoting nuclear translocation of beta-catenin and expression of REG I alpha.