Moscatello D K, Santra M, Mann D M, McQuillan D J, Wong A J, Iozzo R V
Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Clin Invest. 1998 Jan 15;101(2):406-12. doi: 10.1172/JCI846.
Decorin, a small leucine-rich proteoglycan, is capable of suppressing the growth of various tumor cell lines when expressed ectopically. In this report, we investigated the biochemical mechanism by which decorin inhibits cell cycle progression. In A431 squamous carcinoma cells, decorin proteoglycan or protein core induced a marked growth suppression, when either exogenously added or endogenously produced by a transgene. Decorin caused rapid phosphorylation of the EGF receptor and a concurrent activation of mitogen-activated protein (MAP) kinase signal pathway. This led to a protracted induction of endogenous p21, a potent inhibitor of cyclin-dependent kinases, and ultimate cell cycle arrest. Biglycan, a related proteoglycan, had no effect. Moreover, decorin activated the EGF receptor/MAP kinase/ p21 axis in cell lines of various histogenetic backgrounds. These results provide the first evidence that EGF and decorin converge functionally to regulate the cell cycle through activation of a common pathway which ultimately leads to growth suppression.
核心蛋白聚糖是一种富含亮氨酸的小分子蛋白聚糖，当异位表达时能够抑制多种肿瘤细胞系的生长。在本报告中，我们研究了核心蛋白聚糖抑制细胞周期进程的生化机制。在A431鳞状癌细胞中，无论是外源添加核心蛋白聚糖蛋白聚糖或蛋白核心，还是通过转基因内源性产生，均可诱导显著的生长抑制。核心蛋白聚糖导致表皮生长因子（EGF）受体快速磷酸化，并同时激活丝裂原活化蛋白（MAP）激酶信号通路。这导致内源性p21（一种细胞周期蛋白依赖性激酶的有效抑制剂）的长期诱导，并最终导致细胞周期停滞。双糖链蛋白聚糖是一种相关的蛋白聚糖，没有这种作用。此外，核心蛋白聚糖在各种组织发生背景的细胞系中激活EGF受体/MAP激酶/p21轴。这些结果提供了首个证据，即EGF和核心蛋白聚糖在功能上通过激活共同途径来调节细胞周期，最终导致生长抑制。
