RHO-DEPENDENT CELL SPREADING ACTIVATED BY ESCHERICHIA-COLI CYTOTOXIC NECROTIZING FACTOR-1 HINDERS APOPTOSIS IN EPITHELIAL-CELLS

Cell-cell and cell-matrix interactions play a pivotal role in numerous cell functions including cell survival and death, In this work, we re port evidence that the Rho-dependent cell spreading activated by a pro tein toxin from E. coli, the cytotoxic necrotizing factor 1 (CNF1), is capable of hindering apoptosis in HEp-2 cells. In addition to the pro motion of cell spreading, CNF1 protects cells from the experimentally- induced rounding up and detachment and improves the ability of cells t o adhere to each other and to the extracellular matrix by modulating t he expression of proteins related to cell adhesion. In particular, the expression of integrins such as alpha(5), alpha(6) and alpha(v), as w ell as of some heterotypic and homotypic adhesion-related proteins suc h as the Focal Adhesion Kinase, E-cadherin, alpha and beta catenins we re significantly increased in cells exposed to CNF1, Our results sugge st, 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 Rh o, such as Cytochalasin B, was in fact ineffective in favouring cell s urvival. These data are of relevance (i) for the understanding of the role of the actin-dependent and especially Rho-dependent cellular acti vities involved in apoptosis regulation and (ii) in providing some clu es to understanding the mechanisms by which bacteria, by controlling c ell fate, might exert their pathogenic activity.