title: Fucosyltransferase 8 as a functional regulator of nonsmall cell lung cancer.
abstract: The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial-mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.
authors.affiliation: Institute of Biochemical Sciences,  National Taiwan University, Taipei 106,  Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Jan
authors.forename: Yi-Hsiu
authors.initials: YH
authors.lastname: Juan
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Yang
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Hsu
authors.forename: Chi-Huey
authors.initials: CH
authors.lastname: Wong
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D046228:Microarray Analysis; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000503:physiopathology; D014183:Transplantation, Heterologous; D051176:beta Catenin / Q000378:metabolism
chemical_list: C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051176:beta Catenin; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase