title: Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated             behavior in gastric cancer.
abstract: Aberrant glycosylation of cell surface glycoprotein due to specific alterations             of glycosyltransferase activity is usually associated with invasion and metastasis             of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase             2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is             also involved in tumor migration and invasion. However, a comprehensive understanding             of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer             is not currently available. In the present study, ppGalNAc-T2 was detected in             a variety of human poorly differentiated tumor cells, and expression appeared             to be higher in SGC7901 gastric cancer cells. In addition, we investigated the             potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior             in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense             vectors. We found that cell proliferation, adhesion and invasion were decreased             in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated             cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic             activities of ppGalNAc-T2. Further investigation indicated that overexpression             of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2             expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2             suppressing the expression of transforming growth factor (TGF)-β1. However, it             did not exhibit any apparent correlation with MMP-14 expression levels. Our data             show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901             gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative             and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results             indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human             gastric cancer treatment.
authors.affiliation: Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhou
authors.forename: Aihuan
authors.initials: A
authors.lastname: Yue
authors.forename: Shitao
authors.initials: S
authors.lastname: Zou
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Shiliang
authors.initials: S
authors.lastname: Wu
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013274:Stomach Neoplasms; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D000097763:Polypeptide N-acetylgalactosaminyltransferase
chemical_list: D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2; D017350:N-Acetylgalactosaminyltransferases; D053773:Transforming Growth Factor beta1; D000097763:Polypeptide N-acetylgalactosaminyltransferase; C522361:MMP2 protein, human; C507086:MMP14 protein, human