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Articles 1 - 9 of 9
Full-Text Articles in Cell and Developmental Biology
Integrin (Alpha 6 Beta 4) Regulation Of Eif-4e Activity And Vegf Translation: A Survival Mechanism For Carcinoma Cells, Jun Chung, Robin E. Bachelder, Elizabeth A. Lipscomb, Leslie M. Shaw, Arthur M. Mercurio
Integrin (Alpha 6 Beta 4) Regulation Of Eif-4e Activity And Vegf Translation: A Survival Mechanism For Carcinoma Cells, Jun Chung, Robin E. Bachelder, Elizabeth A. Lipscomb, Leslie M. Shaw, Arthur M. Mercurio
Arthur M. Mercurio
We define a novel mechanism by which integrins regulate growth factor expression and the survival of carcinoma cells. Specifically, we demonstrate that the alpha 6 beta 4 integrin enhances vascular endothelial growth factor (VEGF) translation in breast carcinoma cells. The mechanism involves the ability of this integrin to stimulate the phosphorylation and inactivation of 4E-binding protein (4E-BP1), a translational repressor that inhibits the function of eukaryotic translation initiation factor 4E (eIF-4E). The regulation of 4E-BP1 phosphorylation by alpha 6 beta 4 derives from the ability of this integrin to activate the PI-3K-Akt pathway and, consequently, the rapamycin-sensitive kinase mTOR that …
The Integrin Alpha6beta4 Functions In Carcinoma Cell Migration On Laminin-1 By Mediating The Formation And Stabilization Of Actin-Containing Motility Structures, Isaac Rabinovitz, Arthur M. Mercurio
The Integrin Alpha6beta4 Functions In Carcinoma Cell Migration On Laminin-1 By Mediating The Formation And Stabilization Of Actin-Containing Motility Structures, Isaac Rabinovitz, Arthur M. Mercurio
Arthur M. Mercurio
Functional studies on the alpha6beta4 integrin have focused primarily on its role in the organization of hemidesmosomes, stable adhesive structures that associate with the intermediate filament cytoskeleton. In this study, we examined the function of the alpha6beta4 integrin in clone A cells, a colon carcinoma cell line that expresses alpha6beta4 but no alpha6beta1 integrin and exhibits dynamic adhesion and motility on laminin-1. Time-lapse videomicroscopy of clone A cells on laminin-1 revealed that their migration is characterized by filopodial extension and stabilization followed by lamellae that extend in the direction of stabilized filopodia. A function-blocking mAb specific for the alpha6beta4 integrin …
Integrin Alpha 6 Beta 4 Mediates Dynamic Interactions With Laminin, Aydin Tozeren, Hynda K. Kleinman, Stephen Wu, Arthur M. Mercurio, Stephen W. Byers
Integrin Alpha 6 Beta 4 Mediates Dynamic Interactions With Laminin, Aydin Tozeren, Hynda K. Kleinman, Stephen Wu, Arthur M. Mercurio, Stephen W. Byers
Arthur M. Mercurio
We present here a novel form of dynamic adhesion in which both the integrin receptor and the ligand supporting dynamic adhesion have been identified. Laminar flow assays showed that laminin supported attachment of alpha 6 beta 4-positive cells in the presence of fluid shear stress (tau < or = 2 dyn/cm2), indicating that these cells adhered to laminin within a fraction of a second. Further increases in flow rate (3.5 dyn/cm2 < or = tau < or = 100 dyn/cm2) initiated rolling of attached cells in the direction of flow, suggesting that rapidly formed adhesion is reversible and repeatable. Laminin fragment E8, which …
Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren
Role Of E-Cadherin In The Response Of Tumor Cell Aggregates To Lymphatic, Venous And Arterial Flow: Measurement Of Cell-Cell Adhesion Strength, Stephen W. Byers, Connie L. Sommers, Becky Hoxter, Arthur M. Mercurio, Aydin Tozeren
Arthur M. Mercurio
Defects in the expression or function of the calcium dependent cell-cell adhesion molecule E-cadherin are common in invasive, metastatic carcinomas. In the present study the response of aggregates of breast epithelial cells and breast and colon carcinoma cells to forces imposed by laminar flow in a parallel plate flow channel was examined. Although E-cadherin negative tumor cells formed cell aggregates in the presence of calcium, these were significantly more likely than E-cadherin positive cell aggregates to disaggregate in response to low shear forces, such as those found in a lymphatic vessel or venule (< 3.5 dyn/cm2). E-cadherin positive normal breast epithelial cells and E-cadherin positive breast tumor cell aggregates could not be disaggregated when exposed to shear forces in excess of those found in arteries (> 100 dyn/cm2). E-cadherin negative cancer cells …
Human Colon Carcinoma Cells Use Multiple Receptors To Adhere To Laminin: Involvement Of Alpha 6 Beta 4 And Alpha 2 Beta 1 Integrins, Margaret M. Lotz, Cynthia A. Korzelius, Arthur M. Mercurio
Human Colon Carcinoma Cells Use Multiple Receptors To Adhere To Laminin: Involvement Of Alpha 6 Beta 4 And Alpha 2 Beta 1 Integrins, Margaret M. Lotz, Cynthia A. Korzelius, Arthur M. Mercurio
Arthur M. Mercurio
In this study, we used clone A, a human colon carcinoma cell line, to characterize those integrins that mediate colon carcinoma adhesion to laminin. Monoclonal antibodies specific for the human beta 1 subunit inhibited clone A adhesion to laminin. They also precipitated a complex of surface proteins that exhibited an electrophoretic behavior characteristic of alpha 2 beta 1 and alpha 3 beta 1. A monoclonal antibody specific for alpha 2 (PIH5) blocked clone A adhesion to laminin, as well as to collagen I. An alpha 3-specific antibody (P1B5) had no effect on clone A adhesion to laminin, even though it …
P53 Inhibits Alpha 6 Beta 4 Integrin Survival Signaling By Promoting The Caspase 3-Dependent Cleavage Of Akt/Pkb, Robin E. Bachelder, Mark J. Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R. Davis, Arthur M. Mercurio
P53 Inhibits Alpha 6 Beta 4 Integrin Survival Signaling By Promoting The Caspase 3-Dependent Cleavage Of Akt/Pkb, Robin E. Bachelder, Mark J. Ribick, Alessandra Marchetti, Rita Falcioni, Silvia Soddu, Kathryn R. Davis, Arthur M. Mercurio
Arthur M. Mercurio
Although the interaction of matrix proteins with integrins is known to initiate signaling pathways that are essential for cell survival, a role for tumor suppressors in the regulation of these pathways has not been established. We demonstrate here that p53 can inhibit the survival function of integrins by inducing the caspase-dependent cleavage and inactivation of the serine/threonine kinase AKT/PKB. Specifically, we show that the alpha6beta4 integrin promotes the survival of p53-deficient carcinoma cells by activating AKT/PKB. In contrast, this integrin does not activate AKT/PKB in carcinoma cells that express wild-type p53 and it actually stimulates their apoptosis, in agreement with …
The Integrin Alpha 6 Beta 4 Is A Laminin Receptor, Edward C. Lee, Margaret M. Lotz, Glenn D. Steele Jr., Arthur M. Mercurio
The Integrin Alpha 6 Beta 4 Is A Laminin Receptor, Edward C. Lee, Margaret M. Lotz, Glenn D. Steele Jr., Arthur M. Mercurio
Arthur M. Mercurio
In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as …
Release Of Camp Gating By The Alpha6beta4 Integrin Stimulates Lamellae Formation And The Chemotactic Migration Of Invasive Carcinoma Cells, Kathleen L. O'Connor, Leslie M. Shaw, Arthur M. Mercurio
Release Of Camp Gating By The Alpha6beta4 Integrin Stimulates Lamellae Formation And The Chemotactic Migration Of Invasive Carcinoma Cells, Kathleen L. O'Connor, Leslie M. Shaw, Arthur M. Mercurio
Arthur M. Mercurio
The alpha6beta4 integrin promotes carcinoma in-vasion by its activation of a phosphoinositide 3-OH (PI3-K) signaling pathway (Shaw, L.M., I. Rabinovitz, H.H.-F. Wang, A. Toker, and A.M. Mercurio. Cell. 91: 949-960). We demonstrate here using MDA-MB-435 breast carcinoma cells that alpha6beta4 stimulates chemotactic migration, a key component of invasion, but that it has no influence on haptotaxis. Stimulation of chemotaxis by alpha6beta4 expression was observed in response to either lysophosphatidic acid (LPA) or fibroblast conditioned medium. Moreover, the LPA-dependent formation of lamellae in these cells is dependent upon alpha6beta4 expression. Both lamellae formation and chemotactic migration are inhibited or "gated" by …
Protein Kinase C-Dependent Mobilization Of The Alpha6beta4 Integrin From Hemidesmosomes And Its Association With Actin-Rich Cell Protrusions Drive The Chemotactic Migration Of Carcinoma Cells, Isaac Rabinovitz, Alex Toker, Arthur M. Mercurio
Protein Kinase C-Dependent Mobilization Of The Alpha6beta4 Integrin From Hemidesmosomes And Its Association With Actin-Rich Cell Protrusions Drive The Chemotactic Migration Of Carcinoma Cells, Isaac Rabinovitz, Alex Toker, Arthur M. Mercurio
Arthur M. Mercurio
We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the alpha6beta4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express alpha6beta4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the alpha6beta4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis ( approximately 1 ng/ml), the alpha6beta4 integrin is …