Correlation of Deregulated Like-Acetylglucosaminyl Transferase and Aberrant α-Dystroglycan Expression With Human Tongue Cancer Metastasis

PurposeThe present study examined the correlation of α-dystroglycan (α-DG) expression and like-acetylglucosaminyl transferase (LARGE) with metastasis of human tongue cancer.Materials and MethodsFifty human tongue cancer tissues and 2 tongue squamous cell carcinoma cell lines (CAL27 and SCC4) were involved. Immunohistochemistry was used to detect the expression of α-DG and LARGE. Methylation-specific polymerase chain reaction was performed to assess the methylation status of the LARGE gene promoter. CAL27 and SCC4 cells were transfected with exogenous LARGE and treated with 5-aza-2′-deoxycytidine (Aza-dC), respectively. Glycol sites of α-DG were detected by western blotting. In addition, the laminin overlay assay, cell adhesion assay, and invasion assay were performed.ResultsImmunohistochemical results showed that decreased expression of VIA4-1 and IIH6 (antibodies that recognize the glycol sites of α-DG) were correlated with the lymph node metastasis of tongue cancer (n = 50; P = .016 and .025, respectively). Decreased LARGE expression and hypermethylation of the LARGE gene promoter were correlated with lymph node metastasis and α-DG glycosylation in human tongue cancer (n = 50; P = .043 and .015 respectively). In addition, LARGE overexpression and Aza-dC treatment actively led to restoration of functional α-DG expression, elevation of laminin binding, and decrease of migratory ability in cancer cells.ConclusionThe results suggested that absent α-DG expression and LARGE deregulation were closely associated with nodal metastasis of tongue cancer. Aberrant α-DG expression and glycosylation were attributed at least in part to the abnormal epigenetic modification of LARGE, especially the hypermethylation of its promoter.