The Role And Molecular Mechanism Of Fut2 In Regulation Of Colorectal Cancer

Background and Study Aims:Previous studies have identified that colorectal cancer has different fucosylation levels compared to the normal colon.Ulex europaeus agglutinin-I(UEA-I),which specifically combines with al-2 fucose glycan,is usually used to detect fucosylation levels.Therefore,we used confocal laser endomicroscopy(CLE)to investigatefluorescently labeled UEA-Fluorescein isothiocyanate(FITC)for detecting colonic cancer.Patients and Methods:We stained frozen mouse colon tissue sections of normal,adenoma,and adenocarcinoma species with UEA-FITC to detect fucosylation levels in different groups.White light endoscopy and endocytoscopy werefirst used to detect the lesions.The UEA-FITC was then stained in the mice and human colon tissues in vitro.The CLE was used to detect the UEA-FITC levels of the corresponding lesions,and videos were recorded for quantitation analysis.The diagnostic accuracy of UEA-FITC using CLE was evaluated in terms of sensitivity and specificity.Results:The UEA-I expression level in colorectal cancer was lower than that in normal intestinal epithelium.The fluorescence intensity ratio of UEA-FITC in colorectal cancer was significantly lower than that in normal tissue detected by CLE in both mice and humans.The combination of UEA-FITC and CLE presented a good diagnostic accuracy with a sensitivity of 95.6%and a specificity of 97.7%for detecting colorectal cancer.The positive and negative predictive values were 91.6%and 95.6%,respectively.Overall,95.6%of the sites were correctly classified by CLE.Conclusions:We developed a new imaging strategy to improve the diagnostic efficacy of CLE by using UEA-FITC.Background and Study Aims:Our previous study reported that Fut2 deficiency is closely related with colitis.The colitis increases the risk for the development of colorectal cancer(CRC).This study was aimed to investigate the effect and underlying mechanism of Fut2 in CRC.Design:Intestinal epithelium-specific Fut2 knockout(Fut2ΔIEC)mice was used.CRC was induced by azoxymethane(AOM)and dextran sulfate sodium(DSS).Immunofluorescence was applied to examine the level of fucosylation.Proteomics and N-glycoproteomics analysis,UEA-I affinity chromatography,immunoprecipitation,and rescue assay were used to investigate the mechanism of Fut2 in CRCResults:The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissue than that in adjacent normal tissues of AOM/DSS induced CRC mice.More colorectal tumors were detected in Fut2ΔIEC mice compared with control mice,and prominent down regulation of MCAM fucosylation was detected in colorectal tumor tissue of Fut2ΔIEC mice.Overexpression of Fut2 inhibits cell proliferation,invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells.Moreover,fucosylation of MCAM might be a mediator of Fut2 in CRC.Peracetylated 2-F-Fuc,a fucosyltransferase inhibitor,repressed the fucosylation modification of MCAM,reversed the inhibition effects of Fut2 overexpression on SW480 cell proliferation,migration and invasion.Conclusion:Our results indicate that Fut2 deficiency in intestinal epithelium promotes CRC through down-regulating the fucosylation of MCAM.Regulation of fucosylation may be an potential therapy for CRC,especially in those with Fut2 gene defect.