Previous studies have characterized that the ability and possible mechanism involved with β3GnT8 in modulating matrix metalloproteinase-2 (MMP-2) in AGS gastric cancer cells.However, the detailed signal transduction pathway is still little known.In this study, we investigated that β3GnT8 played an important role on the signal transduction pathway during CD147 as an upstream modulator inducing MMPs production in the tumor microenvironment.CD147/basigin/EMMPRIN, a cell surface transmembrane glycoprotein highly expressed in tumor cells, that stimulates matrix metalloproteinases (MMPs) production in neighboring fibroblasts.CD147 shows remarkable variations in size (32-65 kDa) because of heterogeneous N-glycosylation.CD147 has both high and low glycoforms (HG-and LG-CD147),with HG-CD147 containing complex-type carbohydrate and LG-CD147 containing the high-mannose form.The HG-CD147 can induce matrix metalloproteinase (MMPs) production,while the LG-CD147 and purified deglycosylated CD147 fail to induce MMP activity.Here we provide evidence that excess HG-CD147 glycosylation is attributable to GnT-V-generated, 1,6-branched, polylactosamine content.Our evidences illustrate that the glycan of CD147 is important to determine its MMPs expression andβ3GnT8 is involved in the biosynthesis of polylactosamine chains of the HG form of CD147.