The Functions Of Polypeptide N-acetylgalactosaminyltransferase-13 In Lung Cacer And Hepatocellular Carcinoma

O-GalNAc glycosylation is one of the most important post-translational modifications of protein,which is initiated by 20 members of polypeptide N-acetylgalactosaminyltransferases(ppGalNAc-Ts)family.Among the 20 members,ppGalNAc-T13 is restrictively expressed in the brain and lung.It has been reported that ppGalNAc-T13 is a molecular marker of bone marrow involved neuroblastoma and influences the survival of lung cancer patients.However,it remains unclear how ppGalNAc-T13 functions in the lung cancer and whether it participates in the progression of other cancers.Thus,this study is focused on the roles of ppGalNAc-T13 in lung cancer and hepatocellular carcinoma.The first part of this study is focused on the function of ppGalNAc-T13 in lung cancer.The expression of ppGalNAc-T13 did not affect the proliferation of H460 and H1299 cell lines based on the cell viability assay,but showed significant influence on the colony formation.Since the ability of colony formation is deeply associated with the property of cancer cell stemness,we checked the effects of ppGalNAc-T13 on the self-renewal capacity and the drug-resistance ability,both of which are the important phenotypes that reflect cancer cell stemness.Sphere formation and cell viability assays showed that ppGalNAc-T13 contributed to the self-renewal capacity and drug-resistance ability of lung cancer cells.In addition,the expression of ppGalNAc-T13 could activate EGFR and MET pathways,which may provide plausible explanation for the function of ppGalNAc-T13 in the lung cancer.These results indicate that ppGalNAc-T13 may play important roles in the maintenance of stemness property of lung cancer cells,which provided new insights into the functions of ppGalNAc-T13 in the lung cancer.In the second part of this paper,we explored the function of ppGalNAc-T13 in hepatocellular carcinoma due to its differential expression in the nine hepatocellular carcinoma cell lines.It revealed that ppGalNAc-T13 could not only promote the proliferation and migration of hepatocellular carcinoma cell line MHCC-97 L,but also activated the EGFR and ERK pathways.These results suggest that ppGalNAc-T13 may play a role in the progression of hepatocellular carcinoma.Taken together,our studies showed that the high expression of ppGalNAc-T13 contributed to the self-renewal capacity of lung cancer stem cells as well as the drug-resistence ability of lung cancer cells.In addition,we explored the function of ppGalNAc-T13 in the hepatocellular carcinoma.This paper provided a new perspective for understanding the underlying mechanism of ppGalNAc-T13 in the carcinoma progression.