Cell：醣链分子在癌症治疗上的新角色
人体内每个细胞的运作都受控于讯息网(signaling networks)，外来的刺激物由细胞表面的蛋白质接受器(receptor)接收，然后命令细胞分裂或移动等。西奈山(Mount Sinai)医院Samuel Lunenfeld研究院的James Dennis博士发现醣蛋白上醣类的新角色，此开创性的研究发表于顶尖期刊Cell。
人体细胞内有许多重要的蛋白质在转译完成后会由一群复杂的醣类装饰着，研究人员非常明白，当这些醣类的种类因遗传突变或其它变因而被改变时，常与疾病的生成习习相关，例如：癌症、糖尿病或是一些自体免疫疾病，如多发性硬化症等。
目前新一代的抗癌新药，Herceptin（一种抗体）就是以此类目标蛋白作为标靶，来对抗位于乳癌细胞上一种叫做Her-2/neu(或称Erb B-2)的抗原。因Herceptin (商品名Trastuzumab)独特之抗癌疗效及机转，已于1998年九月底经美国药物食品管理局(FDA)核准上市。Dennis研究团队目前仍持续在研究这些重要的醣蛋白，如荷尔蒙或生长因子，以观察这些蛋白质上醣链分子改变对疾病所造成的影响。而此研究发现也将促使更多新型抗癌药物的研发。
(资料来源 : Bio.com)
原始出处: http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=28100017
部分英文原文：
Cell, Vol 129, 123-134, 06 April 2007
Article
Complex N-Glycan Number and Degree of Branching Cooperate to Regulate Cell Proliferation and Differentiation
Ken S. Lau,1,2 Emily A. Partridge,1,3 Ani Grigorian,4 Cristina I. Silvescu,6 Vernon N. Reinhold,6 Michael Demetriou,4,5 and James W. Dennis1,3,
1 Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue R988, Toronto, ON M5G 1X5, Canada
2 Department of Biochemistry, University of Toronto, ON M5S 1A8, Canada
3 Departments of Molecular & Medical Genetics, Laboratory Medicine and Pathology, University of Toronto, ON M5G 1L5, Canada
4 Department of Microbiology and Molecular Genetics, University of California, Irvine, CA 92697-4025, USA
5 Department of Neurology, University of California, Irvine, CA 92862-4280, USA
6 Chemistry, University of New Hampshire, Durham, NH 03824, USA
Corresponding author
James W. Dennis
dennis@mshri.on.ca
The number of N-glycans (n) is a distinct feature of each glycoprotein sequence and cooperates with the physical properties of the Golgi N-glycan-branching pathway to regulate surface glycoprotein levels. The Golgi pathway is ultrasensitive to hexosamine flux for the production of tri- and tetra-antennary N-glycans, which bind to galectins and form a molecular lattice that opposes glycoprotein endocytosis. Glycoproteins with few N-glycans (e.g., TβR, CTLA-4, and GLUT4) exhibit enhanced cell-surface expression with switch-like responses to increasing hexosamine concentration, whereas glycoproteins with high numbers of N-glycans (e.g., EGFR, IGFR, FGFR, and PDGFR) exhibit hyperbolic responses. Computational and experimental data reveal that these features allow nutrient flux stimulated by growth-promoting high-n receptors to drive arrest/differentiation programs by increasing surface levels of low-n glycoproteins. We have identified a mechanism for metabolic regulation of cellular transition between growth and arrest in mammals arising from apparent coevolution of N-glycan number and branching.
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