Fiorentini C, Matarrese P, Straface E, Falzano L, Donelli G, Boquet P, Malorni W
Department of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy.
Cell Death Differ. 1998 Nov;5(11):921-9. doi: 10.1038/sj.cdd.4400422.
Cell-cell and cell-matrix interactions play a pivotal role in numerous cell functions including cell survival and death. In this work, we report evidence that the Rho-dependent cell spreading activated by a protein toxin from E. coli, the cytotoxic necrotizing factor 1 (CNF1), is capable of hindering apoptosis in HEp-2 cells. In addition to the promotion of cell spreading, CNF1 protects cells from the experimentally-induced rounding up and detachment and improves the ability of cells to adhere to each other and to the extracellular matrix by modulating the expression of proteins related to cell adhesion. In particular, the expression of integrins such as alpha 5, alpha 6 and alpha v, as well as of some heterotypic and homotypic adhesion-related proteins such as the Focal Adhesion Kinase, E-cadherin, alpha and beta catenins were significantly increased in cells exposed to CNF1. Our results suggest, however, that the promotion of Rho-dependent cell spreading is the key mechanism in protecting cells against apoptosis rather than cell adhesion per se. A toxin inducing cell spreading without activating Rho, such as Cytochalasin B, was in fact ineffective in favouring cell survival. These data are of relevance (i) for the understanding of the role of the actin-dependent and especially Rho-dependent cellular activities involved in apoptosis regulation and (ii) in providing some clues to understanding the mechanisms by which bacteria, by controlling cell fate, might exert their pathogenic activity.
细胞间和细胞与基质间的相互作用在包括细胞存活和死亡在内的众多细胞功能中起着关键作用。在这项研究中，我们报告了证据表明，由大肠杆菌的一种蛋白质毒素——细胞毒性坏死因子1（CNF1）激活的Rho依赖性细胞铺展能够阻碍HEp - 2细胞的凋亡。除了促进细胞铺展外，CNF1还能保护细胞免受实验诱导的变圆和脱离，并通过调节与细胞黏附相关的蛋白质表达来提高细胞彼此之间以及与细胞外基质黏附的能力。特别是，在暴露于CNF1的细胞中，整合素如α5、α6和αv的表达，以及一些异型和同型黏附相关蛋白质如粘着斑激酶、E - 钙黏蛋白、α和β连环蛋白的表达均显著增加。然而，我们的结果表明，促进Rho依赖性细胞铺展是保护细胞免受凋亡的关键机制，而不是细胞黏附本身。事实上，一种诱导细胞铺展但不激活Rho的毒素，如细胞松弛素B，在促进细胞存活方面是无效的。这些数据对于（i）理解参与凋亡调节的肌动蛋白依赖性尤其是Rho依赖性细胞活动的作用，以及（ii）为理解细菌通过控制细胞命运可能发挥其致病活性的机制提供一些线索具有重要意义。
