癌症葡萄糖机械地启动了整合素介导的生长和生存
Matthew J Paszek1, Christopher C DuFort2, Olivier Rossier3
11] Department of Surgery and Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, California 94143, USA [2] Bay Area Physical Sciences-Oncology Program, University of California, Berkeley, California 94720, USA [3] School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA [4] Laboratory for Atomic and Solid State Physics and Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, New York 14853, USA.
Nature
|July 18, 2014
概括
恶性瘤的特点是重的葡萄糖体,富含大型葡萄糖蛋白. 这种结构增强了细胞粘附和信号传递,可能在晚期癌症中促进转移.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 恶性病与细胞表面甘氨酸和糖蛋白的变化有关.
- 转移性瘤表现出大量甘氨酸蛋白的表达增加,影响细胞甘氨酸.
研究的目的:
- 通过增强整合素粘附和信号传递,调查体积大的糖是否促进瘤表型.
- 确定大型糖蛋白在跨膜受体组织和功能中的作用.
主要方法:
- 开发了一种糖蛋白表达特征,以识别转移性瘤中高调的糖蛋白.
- 利用计算模型预测糖蛋白对受体功能的影响.
- 实验测试了庞大的葡萄糖对人体细胞中整合素粘附,聚类和信号传递的影响.
- 分析了来自晚期疾病患者的循环瘤细胞中的糖蛋白表达.
主要成果:
- 庞大的葡萄糖促进了整合素的聚合,并通过施加压力而改变整合素的状态,独立于actomyosin的收缩性.
- 大型瘤相关糖蛋白在非转化细胞中的表达促进了焦点粘附组合和因特林依赖信号传递.
- 大型葡萄糖蛋白在晚期疾病中的循环瘤细胞上丰富.
结论:
- 重的葡萄糖是瘤细胞的特征,可以增强转移.
- 通过重的糖核糖体机械增强细胞表面受体功能,可能促进瘤细胞的生长,存活和转移.
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