The Function And Mechanism Of Polypeptide N-acetylgalactosaminyltransferases 4 In The Progression Of Colorectal Cancer

Colorectal cancer(CRC)is the third most prevalent cancer worldwide with an increasing incidence in our country.The aberrant expression of O-glycosylation is highly implicated in the cancer malignancy,and associated with intracellular signal transmission,immuno-evasion of the cancer.Polypeptide N-acetylgalactosaminyltransferases(ppGalNAc-Ts)are a family of conserved enzymes that initiate the mucin-type O-glycosylation in cells.In human,up-or down-regulated expression of ppGalNAc-Ts has been frequently observed in multiple types of cancer.However,the function of O-glycosylation and ppGalNAc-Ts in CRC remains obscure.ppGalNAc-T4 is one of the ppGalNAc-Ts family,highly expression of which was found in mucosa and CRC tissues,but there’s few reports about the role of ppGalNAc-T4 in CRC by now.Here,we first investigate the how ppGalNAc-T4 affects the CRC cells via overexpression/knockdown cells.Overexpression of ppGalNAc-T4 in CRC cells enhanced the colony formation and sphere formation but not cell proliferation,suggesting an important role of ppGalNAc-T4 in tumorigenesis.Conversely,knockdown of ppGalNAc-T4 in CRC cells increased the cell migration and invasion,and led to an EMT-like transition.Next,we report that ppGalNAc-T4 shows a dynamic expression at the different stages of colorectal cancer(CRC)in the 62 pair-matched tumor/normal tissues.In detail,ppGalNAc-T4 expression was significantly induced at stage I and II but not at stage III and IV.Further analysis suggested that loss of ppGalNAc-T4 contributed to the dedifferentiation of CRC and correlated to a poor prognosis of patients.Taken together,our results not only demonstrate a dynamic expression of ppGalNAc-T4 at the different stages of CRC,but also suggest that such dynamic expression may contribute to the tumorigenesis at the early stages and promote the cell migration and invasion at the advanced stages.And this study may shed light on the exploration of novel biomarkers and targets for clinical treatment.