title: c-Jun transcriptionally regulates alpha 1, 2-fucosyltransferase 1 (FUT1) in ovarian cancer.
abstract: Alpha 1, 2-fucosyltransferase (FUT 1/2) is a rate-limiting enzyme that catalyzes the synthesis of Lewis y, a cell membrane-associated carbohydrate antigen. In human ovarian cancer, the upregulated expression of FUT1 and Lewis y is associated with advanced pathological stages and involved in cell proliferation, migration and invasion. However, the mechanism underlying the upregulation of FUT1 is largely unknown. Here, we identify an AP-1 binding site in FUT1 promoter in ovarian cancer cells. c-Jun promotes FUT1 expression, thereby enhancing Lewis y biosynthesis in various ovarian cancer cell lines. Moreover, EMSA, luciferase activity and ChIP assays demonstrate c-Jun directly interacts with FUT1 promoter. Furthermore, FUT1 mediates c-Jun-induced cell proliferation in ovarian cancer cells. In human ovarian cancer samples, c-Jun overexpression is linked to malignant degree and positively correlated to FUT1 and Lewis y expression. Taken together, c-Jun could transcriptionally modulate FUT1 expression in ovarian cancer, implicating the potential application of c-Jun inhibitors for human ovarian cancer therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China; Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Dawo
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Biostatistics and Epidemiology, School of Public Health, China Medical University, Shenyang 110001, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Zhuang
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, China. Electronic address: linbei88@hotmail.com.
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D007983:Lewis Blood Group Antigens / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic; D012016:Reference Values; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D005647:Fucosyltransferases; D048031:JNK Mitogen-Activated Protein Kinases; D007983:Lewis Blood Group Antigens; D000097631:Galactoside 2-alpha-L-fucosyltransferase
keywords: FUT1; Lewis y; Ovarian cancer; Transcriptional regulation; c-Jun