Rho-dependent cell spreading activated by E.coli cytotoxic necrotizing factor 1 hinders apoptosis in epithelial cells

Abstract

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 experimentallyinduced 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 a 5 , a 6 and a v , as well as of some heterotypic and homotypic adhesion-related proteins such as the Focal Adhesion Kinase, E-cadherin, a and b 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.

The HIV-1 vpr protein induces anoikis-resistance by modulating cell adhesion process and microfilament system assembly

“…rho A, B and G as well as Rac-1 and Rho GDI (responsible for activation/deactivation cycle of the rho proteins) which are involved in actin filament polymerization and assembly, integrin-mediated cell spreading and cell life and death. 16,17 Our results, reported in Table 2 (bottom) indicated a significant increase of these proteins, particularly of rho B (P50.01), in vpr-expressing cells with respect to control clones. However, the fact that all the rho family proteins considered here appeared to be increased, was also taken into account.…”

“…24,25 Moreover, lack of matrix attachment could stringently restrict inappropriate cell growth by inducing apoptosis in certain histotypes. 9 Consequently, an increase in cell adhesion and spreading, a cytoskeleton associated phenomenon, 16,26 can protect cells against apoptosis. In addition, a specific anti-apoptotic signaling exerted by integrins, particularly a5 and a6, should also be taken into account.…”

Inhibition of Protein Geranylgeranylation and RhoA/RhoA Kinase Pathway Induces Apoptosis in Human Endothelial Cells

“…In addition, Y-27632 inhibited phosphorylation of focal adhesion kinase and the assembly of focal contacts (21,26,48). Moreover, activation of RhoA by CNF-1 increased the expression of focal adhesion kinase and promoted cell spreading (49). Recently, RhoA kinase activation was showed to be required for apoptotic membrane blebbing in NIH 3T3 and Jurkat cells (50,51).…”

C3‐Fullero‐tris‐methanodicarboxylic acid protects epithelial cells from radiation‐induced anoikia by influencing cell adhesion ability

“…In consideration of the importance of cytoskeletal elements in cell adhesion [4,11], a specific analysis was performed on Factin microfilaments and on a cytoskeleton-related intracellular adhesion plaque-associated molecule, i.e. the FAK.…”

“…In particular, UVB radiation generates superoxide anion radicals, intracellular hydrogen peroxide, and hydroxyl radicals [2]. We have previously demonstrated that UVB (1200 J/m 2) induces in A431 epithelial cells cytoskeleton-dependent surface blebbing and the type of apoptosis called anoikia [3,4]. This is an apoptotic process due to the loss of both homotypic and/or heterotypic cell interactions leading to an 'homeless' condition (anoikia) causing cell death [5].…”