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.

Role of the polypeptide N-acetylgalactosaminyltransferase 3 in ovarian cancer progression: possible implications in abnormal mucin O-glycosylation

“…Similarly, GALNT14 knockdown significantly suppresses the cell migration and altered cellular morphology of EOC cells [48], and GALNT1 knockdown inhibits proliferation and tumor growth of bladder cancer cells [49], while GALNT10 expression positively correlates with histological type and degree of differentiation of gastric cancer [50]. In contrast, GALNT2 exerts anti-proliferative and anti-metastatic activity in gastric, brain and hepatocellular carcinomas [51–53], while GALNT9 is positively associated with a better clinical outcome in neuroblastoma patients [54], and GALNT12 expression represents a negative marker especially of metastatic gastric and colorectal cancer [55]. Also, GALNT14 expression correlates with pro-apoptotic drug's sensitivity in pancreatic carcinoma, non-small-cell lung carcinoma and melanoma cell lines [56].…”

Knockdown of GALNT1 suppresses malignant phenotype of hepatocellular carcinoma by suppressing EGFR signaling

“…Altered expressions of GALNT enzymes have been reported to associate with many cancers. GALNT2 down-regulation contributes to HCC cell malignant behaviors and enhances gastric cell proliferation and invasion [11, 12]. GALNT3 is frequently up-regulated in renal cell carcinoma (RCC) and independently predicts high-grade tumor and poor survival [13]; similarly GALNT3 is also up-regulated in high-grade serous epithelial ovarian cancer (EOC) and is correlated with shorter progression-free survival in advanced stage EOC [14].…”

MiR‐206 inhibits proliferation and migration of prostate cancer cells by targeting CXCL11

“…In previous studies, it has been demonstrated that the inflammatory response is an important feature of malignant neoplasms and is important in the genesis, growth, and metastasis of tumors. 32,33 Chemokines are small (∼8-14 kDa) cytokines with a large family, and more than 50 types of chemokines have been identified. 34 The primary function of chemokines is to orchestrate chemokines directional movement as the predominant inflammatory factors.…”