title: Decreased core-fucosylation contributes to malignancy in gastric cancer.
abstract: The object of the study is to identify N-glycan profiling changes associated with gastric cancer and explore the impact of core-fucosylation on biological behaviors of human gastric cancer cells. A total of 244 subjects including gastric cancer, gastric ulcer and healthy control were recruited. N-glycan profiling from serum and total proteins in gastric tissues was analyzed by DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. The abundance of total core-fucosylated residues and the expression of enzymes involved in core-fucosylation were analyzed with lectin blot, quantitative reverse transcription-polymerase chain reaction, western blot, Immunohistochemical staining and lectin-histochemical staining. The recombinant plasmids of GDP-fucose transporter and α-1,6-fucosyltransferase (Fut8) were constructed and transfected into gastric cancer cell lines BGC-823 and SGC-7901. CCK-8 and wound healing assay were used to assess the functional impact of core-fucosylation modulation on cell proliferation and migration. Characteristic serum N-glycan profiles were found in gastric cancer. Compared with the healthy control, a trianntenary structure abundance, peak 9 (NA3Fb), was increased significantly in gastric cancer, while the total abundance of core-fucosylated residues (sumfuc) was decreased. Core-fucosylated structures, peak6(NA2F) and peak7(NA2FB) were deceased in gastric tumor tissues when compared with that in adjacent non-tumor tissues. Consistently, lens culinaris agglutinin (LCA)-binding proteins were decreased significantly in sera of gastric cancer, and protein level of Fut8 was decreased significantly in gastric tumor tissues compared with that in adjacent non-tumor tissues. Upregulation of GDP-Tr and Fut8 could inhibit proliferation, but had no significant influence on migration of BGC-823 and SGC-7901 cells. Core-fucosylation is down regulated in gastric cancer. Upregulation of core-fucosylation could inhibit proliferation of the human gastric cancer cells.
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Yi
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ping-Ting
authors.initials: PT
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Gao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003710:Demography; D018450:Disease Progression; D005260:Female; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism; D054794:Glycomics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D011134:Polysaccharides / Q000097:blood / Q000737:chemistry; D013274:Stomach Neoplasms / Q000097:blood / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D013276:Stomach Ulcer / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing; D005644:alpha-L-Fucosidase / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D011134:Polysaccharides; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D005644:alpha-L-Fucosidase; D019158:N-Acetylneuraminic Acid
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