Glycosylation of Tetraspanin CD151 Defines the Invasive Phenotype of Human Breast Cancer Cells

CD151 belongs to the tetraspanin family and is a transmembrane glycoprotein that forms a complex with integrins. The complex is involved in cancer cell adhesion, growth, migration, and metastasis. Previous studies have shown that CD151 plays distinctly different roles in different types of cancer. Concerning this, we attempted to elucidate the roles that the N-glycosylation of CD151 plays in cell behavior. The expression of CD151 was diverse in different types of cancer cells and was very low in the human breast cancer cell line MCF-7. To clarify the roles of N-glycosylation, we established wild-type CD151 (CD151/WT)-expressing cells and CD151-non-glycosylation mutant (CD151/NQ)-expressing cells in MCF-7 cells, and we found that the tumor growth of CD151/WT was increased, while the invasion activity of CD151/NQ cells was dramatically enhanced without an increment of the cell-surface expression of integrin β1. We also analyzed the glycan structure of CD151 and found that the N-glycan structure of CD151/WT was rich in oligomannose, which is potentially involved in the interaction with integrins according to 3D structural models. In addition, gene expression analyses using public genomics data sets showed that invasive breast cancers exhibit low expression levels of the STT3B gene. STT3B is a key player in the production and modification of N-glycans, and a low level of STT3B therefore results in a predominant expression of non-glycosylated CD151 and in the accumulation of oligomannose-type glycans in CD151. The results suggest that the expression of the non-glycosylated form of CD151 confers an invasive phenotype to cancer cells, and as such, it could be a therapeutic target to block metastasis in breast cancer.