A functional variant rs10409772 in FUT6 promoter regulates colorectal cancer progression through PKA/CREB signaling

• Published in: Translational oncology Vol. 46; p. 102011
• Main Authors: Zhang, Jie, Song, Qibin, Hu, Weiguo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024; Neoplasia Press; Elsevier
• Subjects: Colorectal cancer; FUT6; Original Research; PKA/CREB signaling; Single nucleotide polymorphism; FUT6; PKA/CREB signaling; Single nucleotide polymorphism; Colorectal cancer
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2024.102011

•Genome-wide association studies had identified many single nucleotide polymorphisms of colorectal cancer.•Single nucleotide polymorphisms in promoter region effect the function of genes.•FUT6 is essential for multicellular organisms, its dysregulation leads to a variety of complex diseases.•PKA/CREB signaling is activated in FUT6 over-expressed cells. Fucosyltransferase 6 (FUT6) is overexpressed in colorectal cancer tissue according to TCGA samples and immunohistochemistry results of a tissue microarray. FUT6 effects cell migration, tumor formation and proliferation of colorectal cancer cells in different essays. FUT6 promotes cancer cell proliferation in vitro and colorectal tumorigenesis in vivo by upregulating PKA/CREB pathway activation. Moreover, FUT6 expression is regulated by rs10409772 shown in the luciferase essays, a single nucleotide polymorphism in the promoter of FUT6. Our study suggests that elevated expression of FUT6 promotes PKA/CREB signaling, which in turn augments colorectal carcinogenesis, indicating a potential therapeutic target for colorectal cancer patients with increased FUT6 expression.