Cancer Biomarkers Development Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, South Korea.
Biochem Biophys Res Commun. 2013 Feb 22;431(4):658-63. doi: 10.1016/j.bbrc.2013.01.065. Epub 2013 Jan 26.
N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes the formation of a β1,6-N-acetylglucosamine (GlcNAc) side chain to a core mannosyl residue in N-linked glycoproteins. Besides its direct function of producing aberrant glycoproteins, it promotes cancer progression by its involvement in the stimulation of oncoproteins. Herein, we report that GnT-V guided the transcriptional activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) in cancer cells. The activated MT1-MMP expression had dual effects on cancer progression. It not only promoted proteolytic activity for cancer cells per se, but also led to the activation of MMP-2. Consequently, the activation of the two MMPs triggered by GnT-V intensified the invasive potential. A quantitative analysis using clinical tissues revealed a relatively strong correlation between GnT-V overexpression and MT1-MMP upregulation. In this study, we report for the first time that GnT-V directs cancer progression by modulating MMPs in cancer.
N-乙酰氨基葡萄糖基转移酶 V（GnT-V）是一种酶，可催化 N-连接糖蛋白中核心甘露糖基残基上形成 β1,6-N-乙酰氨基葡萄糖（GlcNAc）侧链。除了其产生异常糖蛋白的直接功能外，它还通过参与刺激癌蛋白促进癌症进展。在此，我们报告 GnT-V 指导癌细胞中转录激活膜型基质金属蛋白酶-1（MT1-MMP）。激活的 MT1-MMP 表达对癌症进展有双重影响。它不仅促进了癌细胞本身的蛋白水解活性，而且还导致 MMP-2 的激活。因此，由 GnT-V 触发的两种 MMP 的激活增强了侵袭潜力。使用临床组织进行的定量分析显示，GnT-V 过表达与 MT1-MMP 上调之间存在较强的相关性。在这项研究中，我们首次报道 GnT-V 通过调节癌症中的 MMP 来指导癌症进展。
