Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer

Aberrant glycosylation of cell surface glycoprotein due to specific alterationsof glycosyltransferase activity is usually associated with invasion and metastasisof cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, isalso involved in tumor migration and invasion. However, a comprehensive understandingof how ppGalNAc-T2 correlates with the metastasic potential of human gastric canceris not currently available. In the present study, ppGalNAc-T2 was detected ina variety of human poorly differentiated tumor cells, and expression appearedto be higher in SGC7901 gastric cancer cells. In addition, we investigated thepotential effects of ppGalNAc-T2 on growth and metastasis-associated behaviorin SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisensevectors. We found that cell proliferation, adhesion and invasion were decreasedin ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulatedcells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastaticactivities of ppGalNAc-T2. Further investigation indicated that overexpressionof ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2suppressing the expression of transforming growth factor (TGF)-β1. However, itdid not exhibit any apparent correlation with MMP-14 expression levels. Our datashow the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferativeand anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These resultsindicate that ppGalNAc‑T2 may be used as a novel therapeutic target for humangastric cancer treatment.