BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization.
BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization.
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BCL 2是一种多功能抗凋亡蛋白。然而，很少有人知道它在细胞粘附和运动事件中的作用。在这里，我们表明，BCL 2可能在细胞粘附，扩散和运动的调节中发挥作用。当BCL 2在培养的鼠和人细胞系中过表达时，细胞的铺展、粘附和运动性受损。与这些结果一致，Bcl 2的缺失导致在Bcl 2缺失小鼠胚胎成纤维细胞中观察到的运动性高于其野生型。BCL 2调节细胞粘附和运动的机制可能涉及形成含有BCL 2、肌动蛋白和凝溶胶蛋白的复合物，其似乎功能性地降低凝溶胶蛋白切断活性。我们已经观察到，在无细胞体外测定中，来自过表达BCL 2的MCF-7细胞和NIH 3 T3细胞的裂解物增强了肌动蛋白聚合。BCL 2和F-肌动蛋白在扩散过程中的共聚焦免疫荧光定位一致表明，BCL 2的表达增加导致F-肌动蛋白聚合增加。因此，BCL 2和凝溶胶蛋白复合物（可能含有其他蛋白质）的形成似乎在细胞粘附和迁移的调节中发挥关键作用。鉴于细胞运动性与癌症转移的相关性，这一结果可以解释为什么BCL 2在某些肿瘤细胞类型中的表达降低了转移的可能性，并改善了患者的预后。
BCL2 is best known as a multifunctional anti-apoptotic protein. However, little is known about its role in cell adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, loss of Bcl2 resulted in higher motility observed in Bcl2 null mouse embryonic fibroblast cells compared to its wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin and gelsolin, which appears to functioally decrease gelsolin-severing activity. We have observed that the lysate from MCF-7 cells and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, formation of BCL2 and gelsolin complexes (which possibly contains other proteins) appears to play a critical role in regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why expression of BCL2 in some tumor cell types reduces the potential for metastasis and shows improved patients prognosis.
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影响因子：
10.4
作者：
Ishido, Masami;Ohtsubo, Rieko;Adachi, Tatsumi;Kunimoto, Manabu
通讯作者：
Kunimoto, Manabu
影响因子：
11.4
作者：
De Corte, V;Bruyneel, E;Gettemans, J
通讯作者：
Gettemans, J
影响因子：
11.2
作者：
DiVito, KA;Berger, AJ;Kluger, HM
通讯作者：
Kluger, HM
影响因子：
2.7
作者：
Gildea, JJ;Harding, MA;Theodorescu, D
通讯作者：
Theodorescu, D
影响因子：
11.4
作者：
Azuma, T;Witke, W;Kwiatkowski, DJ
通讯作者：
Kwiatkowski, DJ