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Titolo:
Shape-dependent control of cell growth, differentiation, and apoptosis: Switching between attractors in cell regulatory networks
Autore:
Huang, S; Ingber, DE;
Indirizzi:
Childrens Hosp, Dept Surg, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 Hosp, Dept Surg, Boston, MA 02115 USA Childrens Hosp, Dept Pathol, Boston, MA 02115 USA Childrens Hosp Boston MA USA 02115 osp, Dept Pathol, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 vard Univ, Sch Med, Boston, MA 02115 USA
Titolo Testata:
EXPERIMENTAL CELL RESEARCH
fascicolo: 1, volume: 261, anno: 2000,
pagine: 91 - 103
SICI:
0014-4827(20001125)261:1<91:SCOCGD>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; CYCLIN D1 EXPRESSION; MAP KINASE; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; GEOMETRIC CONTROL; FOCAL ADHESIONS; MESSENGER-RNA;
Keywords:
cell shape; signal transduction; cytoskeleton; Boolean networks;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
102
Recensione:
Indirizzi per estratti:
Indirizzo: Ingber, DE Childrens Hosp, Dept Surg, Boston, MA 02115 USA Childrens HospBoston MA USA 02115 Surg, Boston, MA 02115 USA
Citazione:
S. Huang e D.E. Ingber, "Shape-dependent control of cell growth, differentiation, and apoptosis: Switching between attractors in cell regulatory networks", EXP CELL RE, 261(1), 2000, pp. 91-103

Abstract

Development of characteristic tissue patterns requires that individual cells be switched locally between different phenotypes or "fates;" while one cell may proliferate, its neighbors may differentiate or die. Recent studieshave revealed that local switching between these different gene programs is controlled through interplay between soluble growth factors, insoluble extracellular matrix molecules, and mechanical forces which produce cell shape distortion. Although the precise molecular basis remains unknown, shape-dependent control of cell growth and function appears to be mediated by tension-dependent changes in the actin cytoskeleton. However, the question remains: how can a generalized physical stimulus, such as cell distortion, activate the same set of genes and signaling proteins that are triggered by molecules which bind to specific cell surface receptors. In this article, we use computer simulations based on dynamic Boolean networks to show that the different cell fates that a particular cell can exhibit may represent a preprogrammed set of common end programs or "attractors" which self-organize within the cell's regulatory networks. In this type of dynamic network modelof information processing, generalized stimuli (e.g., mechanical forces) and specific molecular cues elicit signals which follow different trajectories, but eventually converge onto one of a small set of common end programs (growth, quiescence, differentiation, apoptosis, etc.). In other words, if cells use this type of information processing system, then control of cell function would involve selection of preexisting (latent) behavioral modes of the cell, rather than instruction by specific binding molecules. Importantly, the results of the computer simulation closely mimic experimental dataobtained with living endothelial cells. The major implication of this finding is that current methods used for analysis of cell function that rely oncharacterization of linear signaling pathways or clusters of genes with common activity profiles may overlook the most critical features of cellular information processing which normally determine how signal specificity is established and maintained in living cells. (C) 2000 Academic Press.

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Documento generato il 23/01/21 alle ore 10:05:33