Zavareh, Reza BeheshtiSukhai, Mahadeo A.Hurren, RoseGronda, MarcelaWang, XiaomingSimpson, Craig D.Maclean, NeilZih, FrancisKetela, TroySwallow, Carol J.Moffat, JasonRose, David R.Schachter, HarrySchimmer, Aaron D.Dennis, James W.2026-06-182026-06-182012-09-05https://doi.org/10.1371/journal.pone.0043721https://hdl.handle.net/10012/23638© Beheshti Zavareh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Oncogenic signaling promotes tumor invasion and metastasis, in part, by increasing the expression of tri- and tetra- branched N-glycans. The branched N-glycans bind to galectins forming a multivalent lattice that enhances cell surface residency of growth factor receptors, and focal adhesion turnover. N-acetylglucosaminyltransferase I (MGAT1), the first branching enzyme in the pathway, is required for the addition of all subsequent branches. Here we have introduced MGAT1 shRNA into human HeLa cervical and PC-3-Yellow prostate tumor cells lines, generating cell lines with reduced transcript, enzyme activity and branched N-glycans at the cell surface. MGAT1 knockdown inhibited HeLa cell migration and invasion, but did not alter cell proliferation rates. Swainsonine, an inhibitor of α-mannosidase II immediately downstream of MGAT1, also inhibited cell invasion and was not additive with MGAT1 shRNA, consistent with a common mechanism of action. Focal adhesion and microfilament organization in MGAT1 knockdown cells also indicate a less motile phenotype. In vivo, MGAT1 knockdown in the PC-3-Yellow orthotopic prostate cancer xenograft model significantly decreased primary tumor growth and the incidence of lung metastases. Our results demonstrate that blocking MGAT1 is a potential target for anti-cancer therapy.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/prostate cancerlung and introthoracic tumorsmetastasisccell migrationHeLa cellsmouse modelscell stainingfluorescence imagingArticle