I-branching N-acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling.
Bottom Line: GCNT2-positive cells were significantly lesser in organ-confined disease than in that with extra-capsular extensions, and GCNT2-negative tumors were associated with significantly better prostate-specific antigen-free survival compared with GCNT2-positive tumors.Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion.In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.
Affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.Show MeSH
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Mentions: Interactions between cells and the ECM have been shown to regulate cell motility.23 Moreover, cell surface glycan modifications have reported biological functions during adhesion to the ECM and selectins and inhibits natural killer cell cytotoxicity.24, 25 Thus, we investigated the effects of GCNT2 on cell surface glycans, and confirmed that GCNT2 converts i‐antigen to I‐antigen on cell surface carbohydrate structures (Fig. 1a). Specifically, GCNT2‐expressing PCa cell lines showed pronounced cell surface presentation of I‐antigen (Fig. S3a,b). In contrast, GCNT2 knockdown cells had limited I‐antigen presentation on cell surfaces (Fig. 3a,b). GCNT2 reportedly acts on O‐glycans, N‐glycans, and glycolipids to form GlcNAc‐Gal branches (Fig. 1a).12 Accordingly, after treatment of DU145NC cells with the inhibitors BAG or PPMP, significantly decreased I‐antigen expression was observed. Moreover, co‐treatment with BAG and PPMP led to greater inhibition of I‐antigen presentation than individual treatments (Fig. 3d). In contrast, treatment with TM did not decrease I‐antigen presentation on cell surfaces (Fig. 3c,d). Treatment with these inhibitors decreased each glycan on the cell surface (Fig. S4), suggesting that I‐antigens were formed on O‐glycan and glycolipid molecules on PCa cell surfaces.
Affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.