The polypeptide N‐acetylgalactosaminyltransferase 4 exhibits stage‐dependent expression in colorectal cancer and affects tumorigenesis, invasion and differentiation

The aberrant expression of mucin‐type O‐glycosylation plays important roles in cancer malignancy. The polypeptide N‐acetylgalactosaminyltransferases (ppGalNAc‐Ts) are a family of conserved enzymes that initiate the mucin‐type O‐glycosylation in cells. In human, consistent up‐ or down‐regulation of ppGalNAc‐Ts expression during cancer development has been frequently reported. Here, we provide evidence that ppGalNAc‐T4 shows a stage‐dependent expression at the different stages of colorectal cancer (CRC) in the 62 pair‐matched tumor/normal tissues. In detail, ppGalNAc‐T4 expression is significantly induced at stage I and II but not at stage III and IV. Overexpression of ppGalNAc‐T4 in CRC cells enhances colony formation and sphere formation suggesting an important role of ppGalNAc‐T4 in tumorigenesis. Conversely, knockdown of ppGalNAc‐T4 in CRC cells increases the cell migration and invasion, and leads to an epithelial–mesenchymal transition‐like transition. Further analysis suggests that loss of ppGalNAc‐T4 contributes to the dedifferentiation of CRC and high expression of ppGalNAc‐T4 correlates to a good prognosis of patients. Taken together, our results not only demonstrate a stage‐dependent expression of ppGalNAc‐T4 in CRC progression, but also suggest that such stage‐dependent expression may contribute to the tumorigenesis at the early stage and promote cell migration and invasion at the advanced stage. Polypeptide N‐acetylgalactosaminyltransferases (ppGalNAc‐Ts) are a family of conserved enzymes initiating the mucin‐type O‐glycosylation that plays important roles in cancer malignancy. Here, we found, using 62 pair‐matched tumor/normal tissues, that ppGalNAc‐T4 exhibits stage‐dependent expression in colorectal cancer, which affects tumorigenesis, invasion and differentiation of colorectal cancer. Importantly, low expression of ppGalNAc‐T4 correlates to a poor prognosis of patients.