Decreased Core-Fucosylation Contributes to Malignancy in Gastric Cancer

• Published in: PloS one Vol. 9; no. 4; p. e94536
• Main Authors: Zhao, Yun-Peng, Xu, Xin-Yun, Fang, Meng, Wang, Hao, You, Qing, Yi, Chang-Hong, Ji, Jun, Gu, Xing, Zhou, Ping-Ting, Cheng, Cheng, Gao, Chun-Fang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Abundance; alpha-L-Fucosidase - metabolism; Analysis; Biology and Life Sciences; Biomarkers, Tumor - metabolism; Cancer; Cancer cells; Capillary electrophoresis; Care and treatment; Case-Control Studies; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cholecystokinin; Demography; Deoxyribonucleic acid; Diagnosis; Disease Progression; DNA; Female; Fucose; Fucose - metabolism; Fucosyltransferases - metabolism; Gastric cancer; GDP-fucose; Glycan; Glycomics; Glycoproteins; Hospitals; Human behavior; Humans; Immunoglobulins; Immunohistochemistry; Laboratories; Male; Malignancy; Medicine; Medicine and Health Sciences; Middle Aged; N-Acetylneuraminic Acid - chemistry; N-Acetylneuraminic Acid - metabolism; Nucleotide sequence; Ovarian cancer; Plasmids; Polymerase chain reaction; Polysaccharides - blood; Polysaccharides - chemistry; Prostate; Proteins; Proteomics; Residues; Reverse transcription; Risk factors; Signal transduction; Staining; Stomach cancer; Stomach Neoplasms - blood; Stomach Neoplasms - enzymology; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach Ulcer - metabolism; Stomach Ulcer - pathology; Surgery; Tissues; Tumor cell lines; Tumors; Ulcers; Wound Healing; China; California
• DOI: 10.1371/journal.pone.0094536
• ISSN: 1932-6203

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.