α2β1-integrin signaling by itself controls G1/S transition in a human adenocarcinoma cell line (Caco-2):: implication of NADPH oxidase-dependent production of ROS

α2β1-integrin signaling by itself controls G1/S transition in a human adenocarcinoma cell line (Caco-2):: implication of NADPH oxidase-dependent production of ROS
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DOI:
10.1016/s0014-4827(02)00038-1
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发表时间:
2003-04-15
影响因子:
3.7
通讯作者:
Rognoni, JB
Rognoni, JB
中科院分区:
医学3区
文献类型:
--
作者:
Honoré, S;Kovacic, H;Rognoni, JB

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在这项工作中,我们报道了 IV 型胶原蛋白主要通过 α2β1-整合素连接,能够在无可溶性生长因子或胎牛血清培养的结肠腺癌细胞系 (Caco-2) 中诱导细胞周期蛋白表达和 G1/S 转变。该过程涉及 Erk 1/2 激活以及膜结合 NADPH 氧化酶产生活性氧 (ROS)。这里提供的数据表明,在 α2β1-整合素与 IV 型胶原或特定单克隆抗体 (GO mAb) 连接后,NADPH 氧化酶依赖性 ROS 产生增加。 NADPH 氧化酶的激活以及 ROS 的产生与 α2β1-整合素质膜表达、p38 MAPK 磷酸化、细胞周期蛋白表达和 G1/S 转变的增加有关。因此,我们在这项工作中确定了结肠肿瘤细胞中参与细胞外基质细胞周期调节的新整合素信号传导途径。 (C) 2003 年爱思唯尔科学(美国)。版权所有。
In this work, we report that type IV collagen, mainly via alpha2beta1-integrin ligation, was able to induce cyclin expression and G1/S transition in a colic adenocarcinoma cell line (Caco-2) cultured without soluble growth factors or fetal bovine serum. This process involved Erk 1/2 activation and the production of reactive oxygen species (ROS) by a membrane-bound NADPH oxidase. Data presented here show that NADPH oxidase-dependent production of ROS increased following alpha2beta1-integrin ligation with type IV collagen or with a specific monoclonal antibody (GO mAb). NADPH oxidase activation and, therefore, the production of ROS were shown to be involved in the increase of alpha2beta1-integrin plasma membrane expression, p38 MAPK phosphorylation, cyclin expression, and G1/S transition. We thus identified in this work a new integrin-signaling pathway in colon tumor cells involved in cell cycle regulation by the extracellular matrix. (C) 2003 Elsevier Science (USA). All rights reserved.