FUT2 promotes the tumorigenicity and metastasis of colorectal cancer cells via the Wnt/β‑catenin pathway

Abstract

The incidence of colorectal cancer (CRC), a leading cause of cancer-related mortality, has increased globally. Fucosyltransferase 2 (FUT2), catalyzing the α1, 2-linked fucose in mammals, has been reported to be overexpressed in several malignant cancers, including CRC. However, the effects of FUT2 on CRC remain largely unknown. Herein, it was determined that the FUT2 expression levels in CRC tissues were higher than those in adjacent non-tumor tissues, whereas no association with tumor stage was revealed. The results of biological functional analysis revealed that FUT2 knockdown inhibited the proliferation, migration and invasion of human CRC cells. Moreover, the knockdown of FUT2 arrested the CRC cells at the G0/G1 phase and promoted the apoptosis of human CRC cells. Western blot analysis demonstrated that the expression levels of β-catenin, C-myc and cyclin D1 were decreased by FUT2 knockdown in CRC cells, whereas the expression of glycogen synthase kinase-3β and the phosphorylation levels of β-catenin were increased. Additionally, Wnt2 was fucosylated by FUT2 in CRC cells. Furthermore, the knockdown of FUT2 inhibited the growth of human CRC in vivo. Overall, the findings of the present study suggest that FUT2 may be used as a potential diagnostic biomarker and therapeutic target for CRC treatment.

FUT2 promotes colorectal cancer metastasis by reprogramming fatty acid metabolism via YAP/TAZ signaling and SREBP-1

“…We previously reported that FUT2 is upregulated in clinical CRC tissue, compared to matched normal tissues from the same patients [18]. Here, the data from TCGA and GTEx databases revealed that FUT2 gene expression is elevated in CRC tumors compared to normal colorectal tissues (Fig.…”

“…Xenograft nude mouse model was performed as previously described [18]. Tumors were stored in liquid nitrogen for further experiments.…”

“…Accordingly, the dysregulation of glycosyltransferase has been extensively studied in CRC, and altered gene expression of glycosyltransferases, as well as mutations, have been described for CRC tumor tissues and cell lines [39]. Our previous study has showed that FUT2 was upregulated in CRC and acted as an oncogene in the progression of CRC, and knockdown of FUT2 markedly suppressed cell proliferation, colony formation, migration and invasion [18].…”

“…Researchers have showed that fucosyltransferases were abnormally regulated in CRC and linked to multiple aspects of cancer pathology [17]. Our prior research found that fucosyltransferase 2 (FUT2), responsible for addition of fucose in α-1,2 linkage at glycan terminals, was upregulated in CRC, and promoted the progression of CRC [18]. However, the role of FUT2 in CRC metastasis is unclear.…”

Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer

“…Intriguingly, the tumor-promoting FUT2 and FUT8 expression was highly expressed in tumor colon cE02, cE03, and cE06 epithelial subsets in aging colon tumor. Increased FUT2 and FUT8 expression has been linked to cancer ( 45 , 46 ). Additionally, older patients with a tumor exhibited elevated FUT2, FUT3, and FUT8 coexpression with tumor-promoting IL6ST, IL22RA1, TGFB1, and TGFBR1 genes compared with young tumor.…”