Yoshimura M, Ihara Y, Matsuzawa Y, Taniguchi N
Department of Biochemistry and the Second Department of Internal Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan.
J Biol Chem. 1996 Jun 7;271(23):13811-5. doi: 10.1074/jbc.271.23.13811.
Introduction of the beta1-4 N-acetylglucosaminyltransferase (GnT-III) gene was reported to suppress metastasis in highly metastatic B16-hm murine melanoma cells (Yoshimura, M., Nishikawa, A. , Ihara, Y., Taniguchi, S., and Taniguchi, N.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8754-8758). In this study, the effect of GnT-III gene transfer on E-cadherin was studied, since E-cadherin acts as a suppressor of metastasis. E-cadherin expression at cell-cell contacts of B16-hm cells expressing high GnT-III activity was greater than controls without affecting transcription. Lectin blotting showed that E-cadherin from GnT-III transfectants was glycosylated by ectopically expressed GnT-III. The glycosylated E-cadherin exhibited the delayed turnover and the decreased release from cell surface, as compared with the native E-cadherin, resulting in the elevated expression at the cell-cell border of GnT-III transfectants. Furthermore, cell-cell aggregation was enhanced in GnT-III transfectants, indicating that the glycosylated E-cadherin is biologically functional. These results suggest that the glycosylated E-cadherin contributes to the suppression of metastasis by the introduction of GnT-III gene into melanoma cells.
据报道，β1-4 N-乙酰氨基葡萄糖转移酶（GnT-III）基因的导入可抑制高转移性B16-hm小鼠黑色素瘤细胞的转移（Yoshimura, M., Nishikawa, A., Ihara, Y., Taniguchi, S., and Taniguchi, N. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8754 - 8758）。在本研究中，研究了GnT-III基因转移对E-钙黏蛋白的影响，因为E-钙黏蛋白起着转移抑制因子的作用。在表达高GnT-III活性的B16-hm细胞的细胞间接触处，E-钙黏蛋白的表达高于对照，且不影响转录。凝集素印迹显示，来自GnT-III转染子的E-钙黏蛋白被异位表达的GnT-III糖基化。与天然E-钙黏蛋白相比，糖基化的E-钙黏蛋白表现出周转延迟和从细胞表面释放减少，导致GnT-III转染子的细胞间边界处表达升高。此外，GnT-III转染子中的细胞间聚集增强，表明糖基化的E-钙黏蛋白具有生物学功能。这些结果表明，糖基化的E-钙黏蛋白通过将GnT-III基因导入黑色素瘤细胞而有助于抑制转移。
