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

Abstract

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 β-catenin/REG Iα 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 β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-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 β-catenin nuclear translocation and REG Iα expression.

Moutai Distiller's grains Polyphenol extracts and rutin alleviate DSS-induced colitis in mice: Modulation of gut microbiota and intestinal barrier function （R2）

“…Gut microbiota dysregulation may precipitate intestinal epithelial cell dysfunction and mucosal damage, instigating intestinal inflammation. Moreover, alterations in the gut microbiota alterations may potentiate colitis-related tumorigenesis through the perpetuation of chronic inflammation and the production of carcinogens [ [ 35 ]]. Existing literature suggests that rutin can palliate DSS-induced colonic inflammation in mice by impeding the production and activation of inflammatory mediators, modulating immune cell activity and cytokine secretion, and bolstering the intestinal mucosal barrier to mitigate intestinal inflammation.…”

Regulatory effects of oral microbe on intestinal microbiota and the illness

“…F. nucleatum modifies colonic Th17 cell frequency and IL-17 expression recombinant free fatty acid receptor 2 (FFAR2)-dependently ( Brennan et al., 2021 ). Moreover, it positively correlated with the expression of Wnt-β-catenin (activated by FadA─E-cadherin) and REG Iα signaling, both of which effectively promotes the proliferation of sessile serrated adenoma/polyp ( Rubinstein et al., 2013 ; Nishimura et al., 2021 ). ENO1 gene and ANGPTL4 protein enhance the high glycolysis of colorectal cancer cells, and these two regulatory mechanisms could be upregulated by F. nucleatum either, which further support F. nucleatum colonization and positively collated with poor prognosis ( Hong et al., 2021 ; Zheng et al., 2021 ).…”

A New Comorbidity in Periodontitis: Fusobacterium nucleatum and Colorectal Cancer

“…Recent evidence has also confirmed that fusobacteria are able to reach metastases from the primary tumour or from the oral cavity mainly via the circulatory system rather than the gastrointestinal tract [44]. Nishimura et al demonstrated that Fn might play a role in the proliferation of sessile serrated adenoma/polyp through promoting the β-catenin nuclear translocation and regenerating gene (REG) Iα overexpression [45]. REG is a family of proteins that have a cellular proliferative and antiapoptotic effect on inflamed or neoplastic lesions of the gastrointestinal tract [46].…”