Integrating with integrins.

Abstract

Our central claim is that signaling by integrins provides a mechanism by which signals generated in response to adhesion, soluble hormones, and mechanical forces can interact. Such interactions permit cells to integrate these different classes of external stimuli and hence to orchestrate an efficient response. This integrating function of integrins is likely to be essential for much of development and physiology, as well as complex pathologies such as cancer. Understanding in detail how these signals are transduced and processed is likely to be an important area of research in the near future.

Adhesive Mechanisms Regulating Invasion and Metastasis in Oral Cancer

“…In a third report, cleavage of the globular domain of the 03 subunit of laminin-5 converts this extracellular protein from a cell-motility-inducing factor to a protein complex that can trigger formation of the stationary structures referred to as hemidesmosomes, thus preventing cell movement (Goldfinger et al, 1999). Recently, researchers reported that laminin-5 can trigger disruption of cell-cell junctions and induce scattering of oral SCC cells (Kawano et al, 2001 (Hynes, 1992 (Hynes, 1992;Schwartz and Ingber, 1994).…”

Connecting signaling and cell cycle progression in growth factor-stimulated cells

“…Integrins are a family of cell surface receptors consisting of heterodimers between a and b subunits that mediate attachment of cells to extracellular matrix (ECM) proteins such as ®bronectin and collagen (Clark and Brugge, 1995;Schwartz and Ingber, 1994). The intracellular domains of integrin molecules not only physically link the plasma membrane to the cytoskeleton, but also initiate signaling cascades.…”

“…In addition, the nature of the ECM onto which cells are plated (and hence the types of integrins that are engaged) can enhance or diminish the mitogenic potency of growth factors Schneller et al, 1997). Finally, compromising the contribution of integrins by suspending a population of adherent cells alters some of the signaling pathways triggered by growth factors, and prevents cell cycle progression (Assoian, 1997;Clark and Brugge, 1995;Schwartz and Ingber, 1994). The growth factor promotes tyrosine phosphorylation of Shc and hence it association with Grb2 via the SH2 domain of Grb2.…”

Melanoma cell migration to type IV collagen requires activation of NF-κB

“…Integrin ligation and clustering alter the cytoskeleton and initiates the assembly of a molecular platform upon which signaling molecules including src-kinases, GTPases, and various adapters are recruited to form focal adhesion complexes (Schwartz and Ingber, 1994;Schaller and Parsons, 1994;Schwartz et al, 1995;Meredith et al, 1996;Renshaw et al, 1996;Keely et al, 1998;Price et al, 1998;Giancotti and Ruoslahti, 1999;Parsons et al, 2000;Salazar and Rozengurt, 2001). Furthermore, the engagement of a2b1 integrin by CIV has been shown to increase intracellular Ca 2+ (Savarese et al, 1992;Leavesley et al, 1993;Hodgson and Dong, 2001).…”