Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts.

Regen, Chester M.; Horwitz, Alan E

doi:10.1083/jcb.119.5.1347

Cited by 204 publications

(180 citation statements)

References 39 publications

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“…As a result, a gradient of adhesive strength are created from the front to the rear of the migrating cell, allowing the cell to advance over its substrate. 16,48,49 Optimal migration, therefore, requires coordination between the formation of new adhesions at the cell front and their subsequent release at the cell rear. Agents that perturb this delicate balance of adhesion and release therefore inhibit cell migration.…”

Section: Discussionmentioning

confidence: 99%

Role of ?1 integrins in adhesion and invasion of hepatocellular carcinoma cells

1999

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To investigate the role of integrins in hepatocellular carcinoma (HCC) invasion, we analyzed the relationship between the expression and activity of ␤1 integrins and the invasive ability of multiple HCC cell lines. Human HCC cell lines, PLC/PRF/5, Hep3B, HepG2, HLE, HuH7, and C3A cells, had high expression of ␤1 and ␣6 subunits, and various levels of ␣1, ␣2, ␣3, and ␣5 expression as determined by cell surface flow cytometry. Activity of ␤1 integrins was evaluated by cell adhesion to collagen, fibronectin, and laminin in the presence or absence of the stimulatory anti-␤1 monoclonal antibody ( Tumor invasion and metastasis are complex processes requiring the ability of tumor cells to interact with endothelial cells and extracellular matrix. The major cell surface receptors that mediate these interactions are integrins. They are heterodimeric transmembrane receptors consisting of ␣ and ␤ subunits, which produce more than 20 different heterodimers and bind specific ligands. 1,2 Each subunit is a glycoprotein with a large extracellular domain and a relatively small cytoplasmic domain. It has been shown that integrins can transduce signals and play principal roles in biological features of tumors, especially in growth, differentiation, and invasive and metastatic events of malignant cells. 2,3 Changes in expression of integrins have been linked to both tumor suppression and tumor progression in different human malignancies. 4,5 Several studies have described altered expression of ␤1 integrins in hepatocellular carcinoma (HCC). Reduced expression of ␣2, ␣3, and ␣5 subunits 6,7 and overexpression of ␣6 subunits of ␤1 integrins 8 have been shown in HCC with aggressive phenotypes. Nonpolarized aberrant distribution of ␤1 subunit has been shown to correlate with tumor growth rate, grade, and size in HCC. 9 These observations suggest important roles of ␤1 integrins in growth and invasiveness of HCC. Recently, several studies have indicated the modulation of expression and function of ␤1 integrins on HCC cells during metastatic events. Following the adhesion to vascular endothelial cells, HCC cells receive stimulation from cytokines produced by the endothelial cells. The resultant increase of ␣2␤1 integrin expression on HCC cells may facilitate migration of these cells to extravascular tissues. 10 On the contrary, the cell adhesion regulator, the gene of which is located on 16q, suppresses the process of integrin-mediated cell adhesion and has an inhibitory effect on the progression of HCC. 11

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Section: Discussionmentioning

confidence: 99%

Role of ?1 integrins in adhesion and invasion of hepatocellular carcinoma cells

1999

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“…The invadopodia have been characterized as highly dynamic structures where proteolytic degradation takes place (Chen, 1996;Chen and Wang, 1999;Mueller et al, 1999). Localized matrix degradation takes place also in the leading edge of the membrane extensions together with concomitant formation of nascent adhesive contacts by integrins and other adhesion molecules Regen and Horwitz, 1992). These nascent adhesive sites may further develop to mature focal contacts, which are a highly dynamic protein network containing over fifty different proteins (Zamir and Geiger, 2001).…”

Section: Regulation Of Cell Migrationmentioning

confidence: 99%

Gelatinase-mediated migration and invasion of cancer cells

Björklund

Koivunen

2005

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

463

609

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“…Cells contain significant amounts of integrin that is mobile in the plasma membrane (23) and that redistributes during the formation of new attachment sites (e.g., references 17,22,58,66). The integrin in type I aggregates of Xenopus fibroblasts is probably immobile, as observed at focal contacts in other cells (23; see also reference 27).…”

Section: Significancementioning

confidence: 99%

Structures linking microfilament bundles to the membrane at focal contacts

Samuelsson

Luther

Pumplin

et al. 1993

The Journal of Cell Biology

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Abstract. We used quick-freeze, deep-etch, rotary replication and immunogold cytochemistry to identify a new structure at focal contacts. In Xenopus fibroblasts, elongated aggregates of particles project from the membrane to contact bundles of actin microfilaments. Before terminating, a single bundle of microfilaments interacts with several aggregates that appear intermittently over a distance of several microns. Aggregates are enriched in proteins believed to mediate actin-membrane interactions at focal contacts, including B~-integrin, vinculin, and talin, but they appear to contain less t~-actinin and filamin. We also identified a second, smaller class of aggregates of membrane particles that contained/~-integrin but not vinculin or talin and that were not associated with actin microfilaments. Our results indicate that vinculin, talin, and ~-integrin are assembled into distinctive structures that mediate multiple lateral interactions between microfilaments and the membrane at focal contacts.F OCAL contacts are specialized structures where actin filaments converge and terminate at the plasma membrane (16,32,44,63,65). Interactions between the membrane and microfilaments involve several proteins that are concentrated at focal contacts, including integrin (e.g., references 17, 21, 22; reviewed in 1, 61) and cytoskeletal proteins such as vinculin (26), talin (13), fimbrin (9), tensin (71), paxillin (68), zyxin (5), and ot-actinin (40). Biochemical studies have suggested several ways in which these proteins could anchor microfilaments to the cytoplasmic surface of the plasma membrane at focal contacts. Early studies suggested that particular isoforms of integrin ("CSAT'; 47) bound talin, and that this complex then bound vinculin (35; reviewed in 15). Later studies showed that integrins could also bind tx-actinin (53). Thus, integrin could anchor actin filaments indirectly through the actin-binding protein, tx-actinin, as well as through talin and vinculin. If both of these mechanisms are important for actin-membrane interactions, one would expect all these proteins to be concentrated at focal contacts.Structural studies also suggest two models for microfilament-membrane interactions at focal contacts. Focal contacts are several microns long, and individual actin filaments course over this entire distance before terminating (8). These filaments could bind to the membrane laterally as they approach their termini. In this case, vinculin, talin, integrin, and other proteins of focal contacts would be expected to concentrate at many points along the filament length. Alter- natively, filaments could attach only at their termini. In this case, the proteins of focal contacts would be expected to occur only at the ends of microfilaments.Predictions of the relationship between actin microfilaments and the membrane, and of the distribution of proteins at focal contacts, can be tested by ultrastructural methods coupled with immunocytochemistry. We exposed the cytoplasmic surfaces of ventral membrane by mechanical shearing, the...

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Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts.

Cited by 204 publications

References 39 publications

Role of ?1 integrins in adhesion and invasion of hepatocellular carcinoma cells

Role of ?1 integrins in adhesion and invasion of hepatocellular carcinoma cells

Gelatinase-mediated migration and invasion of cancer cells

Structures linking microfilament bundles to the membrane at focal contacts

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