Growth control by intracellular tension and extracellular stiffness.
Integrin-mediated cell attachment to the extracellular matrix is an established regulator of the cell cycle, and the best-characterized targets of this process are the cyclin D1 gene and members of the cip and kip (cip/kip) family of cdk inhibitors. Manipulation of intracellular tension affects the same targets, supporting the idea that integrin activation and intracellular tension are closely related. Several signaling cascades, including FAK, Rho GTPases and ERK, transmit the integrin and tensional signals to pathways controlling the cell cycle. However, the experimental approaches that have generated these results alter cell adhesion and tension in ways that do not reflect the subtlety of those occurring in vivo. Increasing emphasis is therefore being placed on approaches that use micropatterning to control cell spreading, and deformable substrata to model the compliance of biological tissue.
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6084, USA. assoian@mail.med.upenn.edu
Richard K
RK
Assoian
Eric A
EA
Klein
D000199:Actins / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D004791:Enzyme Inhibitors; D016023:Integrins; D019938:Cyclin D1; D048049:Extracellular Signal-Regulated MAP Kinases; D020741:rho GTP-Binding Proteins