{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Fucosyltransferase 6 (FUT6) is a key glyco‐enzyme that catalyzes the addition of fucose in an α1,3‐linkage to growing glycan chains, thereby modulating the synthesis and structure of complex glycoconjugates. In lung cancer models, for instance, increased expression of FUT6 together with FUT4 enhances fucosylation of the epidermal growth factor receptor (EGFR), which attenuates EGFR dimerization and phosphorylation and ultimately suppresses EGFR‐mediated invasion of lung cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Genetic studies in large human cohorts have further demonstrated that common variants in FUT6 influence plasma N‐glycan profiles, underscoring its broad role in the modulation of protein glycosylation with important implications for immunity, embryonic development, and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In the context of tumor metastasis, FUT6 participates in the formation of sialyl Lewis x determinants on cancer cells, which serve as critical ligands for E‐selectin expressed by bone vascular endothelial cells, and thus promote mesenchymal‐epithelial transition and activate pathways such as Wnt signaling to facilitate bone colonization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In gastrointestinal carcinomas, transcriptional upregulation of FUT6 is associated with increased expression of sialyl Lewis epitopes, which are involved in the synthesis of key selectin ligands that modulate cell adhesion and tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Conversely, in breast cancer studies, reduced expression of FUT6—mediated by the overexpression of oncogenic microRNAs such as miR‐106b—leads to enhanced migration, invasion, and proliferation of cancer cells, suggesting that under certain conditions, FUT6 may function to restrain these malignant behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In hepatocellular carcinoma, however, overexpression of FUT6 has been shown to promote cell cycle progression and tumor growth by activating the PI3K/Akt signaling pathway and downregulating cell cycle inhibitors like p21."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, genetic analyses in specific populations have linked FUT6 variants with metabolic traits such as type 2 diabetes, indicating that alterations in FUT6 activity may have multifaceted physiological consequences."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Finally, associations at the FUT6‐FUT3 locus have been implicated in modulating levels of clinically relevant biomarkers such as CA 19‐9 and carcinoembryonic antigen, further highlighting the clinical impact of FUT6‐mediated glycosylation alterations in malignant settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, FUT6 plays a context‐dependent role in regulating the glycosylation of key cell surface proteins and receptors. Through its enzymatic activity, FUT6 influences cell signaling, adhesion, and metastatic behavior in various cancers and is also implicated in the modulation of plasma glycome profiles and metabolic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ying-Chih Liu, Hsin-Yung Yen, Chien-Yu Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1107385108"}], "href": "https://doi.org/10.1073/pnas.1107385108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21709263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21709263"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gordan Lauc, Abdelkader Essafi, Jennifer E Huffman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1α as a master regulator of plasma protein fucosylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001256"}], "href": "https://doi.org/10.1371/journal.pgen.1001256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21203500"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21203500"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Mark Esposito, Nandini Mondal, Todd M Greco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bone vascular niche E-selectin induces mesenchymal-epithelial transition and Wnt activation in cancer cells to promote bone metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41556-019-0309-2"}], "href": "https://doi.org/10.1038/s41556-019-0309-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30988423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30988423"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "A S Carvalho, A Harduin-Lepers, A Magalhães, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of alpha-2,3-sialyltransferases and alpha-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in gastrointestinal carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2009.09.010"}], "href": "https://doi.org/10.1016/j.biocel.2009.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19781661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19781661"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nana Li, Yuejian Liu, Yuan Miao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-106b targets FUT6 to promote cell migration, invasion, and proliferation in human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "IUBMB Life (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/iub.1541"}], "href": "https://doi.org/10.1002/iub.1541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27519168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27519168"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qiya Guo, Bin Guo, Yingming Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional analysis of α1,3/4-fucosyltransferase VI in human hepatocellular carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.11.106"}], "href": "https://doi.org/10.1016/j.bbrc.2011.11.106"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22155250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22155250"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Feifei Zhao, Dolikun Mamatyusupu, Youxin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Uyghur population and genetic susceptibility to type 2 diabetes: potential role for variants in CAPN10, APM1 and FUT6 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.12911"}], "href": "https://doi.org/10.1111/jcmm.12911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27374856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27374856"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Meian He, Chen Wu, Jianfeng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome wide association study of genetic loci that influence tumour biomarkers cancer antigen 19-9, carcinoembryonic antigen and α fetoprotein and their associations with cancer risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gut (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/gutjnl-2012-303434"}], "href": "https://doi.org/10.1136/gutjnl-2012-303434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23300138"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23300138"}]}]}]}