Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Rodrı́guez-Fernández, José Luis; Geiger, Benjamin; Salomon, Daniela; Sabanay, Ilana; Zöller, Margot; Ben-Ze’ev, Avri

doi:10.1083/jcb.119.2.427

Cited by 211 publications

(99 citation statements)

References 41 publications

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“…8,compare C and D with A and B). These properties are similar to those characteristic of transformed 3T3 cells with diminished vinculin levels (Rodrfguez Fermindez et al, 1992a).…”

Section: Motility and Growth Properties Of Antisense Vinculin-transfesupporting

confidence: 64%

Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells

Fernández

Geiger

Salomon

et al. 1993

The Journal of Cell Biology

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181

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Abstract. The expression of vinculin, a major component of adhesion plaques and cell-cell junctions, is markedly modulated in cells during growth activation, differentiation, motility and cell transformation. The stimulation of quiescent cells by serum factors and the culturing of cells on highly adhesive matrices induce vinculin gene expression, whereas the transformation of fibroblast and epithelial cells often results in decreased vinculin expression (reviewed in Rodrfguez Fermindez, J. L., B. Geiger, D. Salomon, I. Sabanay, M. Z611er, and A. Ben-Ze'ev. 1992. J. Cell Biol. 119:427). To study the effect of reduced vinculin expression on cell behavior, 3T3 cells were transfected with an antisense vinculin cDNA construct, and clones displaying decreased vinculin levels down to 10-30% of control levels were isolated. These cells showed a round phenotype with smaller and fewer vinculin-positive plaques localized mostly at the cell periphery. In addition, they displayed an increased motility compared to controls, manifested by a faster closure of "wounds" introduced into the monolayer, and by the formation of longer phagokinetic tracks. Moreover, the antisense transfectants acquired a higher cloning efficiency and produced larger colonies in soft agar than the parental counterparts. The results demonstrate that the regulation of vinculin expression in cells can affect, in a major way, cell shape and motility, and that decreased vinculin expression can induce cellular changes reminiscent of those found in transformed cells.

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“…8,compare C and D with A and B). These properties are similar to those characteristic of transformed 3T3 cells with diminished vinculin levels (Rodrfguez Fermindez et al, 1992a).…”

Section: Motility and Growth Properties Of Antisense Vinculin-transfesupporting

confidence: 64%

Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells

Fernández

Geiger

Salomon

et al. 1993

The Journal of Cell Biology

Self Cite

181

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“…BSp73ASML cells adhered more strongly to D5.7A + cells and adhesion was signi®cantly augmented by trypsine treatment. Notably, BSp73ASML cells are known to display on a completely disorganized cytoskeleton and are missing vinculin (Matzku et al, 1985;Rodriguez-Fernandez et al, 1992). Next to mention, BSp73ASML cells express a whole set of surface molecules, which are not detected on the non-metastatic lines (Matzku et al, 1989;Claas et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Würfel

Rösel

Seiter³

et al. 1999

Oncogene

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Screening for surface molecules expressed by metastasizing rat tumors had revealed evidence for metastasisassociation of a molecule also expressed on epithelial cells. The similarity to the expression pro®le of the panepithelial glycoprotein EGP314 prompted us to isolate and sequence the gene and to explore functional features of the molecule in transfected tumor lines. The molecule D5.7A, named according to the antibody, D5.7, used for selection, indeed, is the ortholog of EGP314 with 92% and 80% identity to the murine and the human molecules. Like EGP314, D5.7A has a particular cleavage site, a small cleavage product being resolved under reducing conditions from the membrane anchored part of the molecule. Transfection of a low metastasizing ®brosarcoma, pheochromoblastoma and adenocarcinoma revealed that expression of D5.7A facilitates tumor progression. Depending on the origin of the tumor, D5.7A transfectants either metastasized via the lymphatic system (pheochromoblastoma, adenocarcinoma) or hematogeneously (®brosarcoma). Particularly after proteolytic cleavage, D5.7A facilitated cell ± cell adhesion and provided a proliferative signal upon crosslinking. Thus, the rat ortholog of EGP314 is involved in metastasis formation. Importantly, its functional activities apparently rely on proteolytic cleavage. These ®ndings provide a ®rst evidence on how a panepithelial marker can be involved in tumor progression.

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“…Cells were labeled overnight with l[ 35 S]methionine at 100 Ci/ml in methionine-free RPMI 1640 containing 5% FCS, as described previously (Rodríguez-Fernández et al, 1992). Labeled proteins were used to immunoprecipitate FAK with the C-20 antibody.…”

Section: Metabolic Labeling and Autoradiographymentioning

confidence: 99%

The Interaction of Activated Integrin Lymphocyte Function-associated Antigen 1 with Ligand Intercellular Adhesion Molecule 1 Induces Activation and Redistribution of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 in T Lymphocytes

Rodrı́guez-Fernández

Gómez

Luque

et al. 1999

MBoC

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Integrin receptors play a central role in the biology of lymphocytes, mediating crucial functional aspects of these cells, including adhesion, activation, polarization, migration, and signaling. Here we report that induction of activation of the ␤2-integrin lymphocyte function-associated antigen 1 (LFA-1) in T lymphocytes with divalent cations, phorbol esters, or stimulatory antibodies is followed by a dramatic polarization, resulting in a characteristic elongated morphology of the cells and the arrest of migrating lymphoblasts. This cellular polarization was prevented by treatment of cells with the specific tyrosine kinase inhibitor genistein. Furthermore, the interaction of the activated integrin LFA-1 with its ligand intercellular adhesion molecule 1 induced the activation of the cytoplasmic tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK-2). FAK activation reached a maximum after 45 min of stimulation; in contrast, PYK-2 activation peaked at 30 min, declining after 60 min. Upon polarization of lymphoblasts, FAK and PYK-2 redistributed from a diffuse localization in the cytoplasm to a region close to the microtubule-organizing center in these cells. FAK and PYK-2 activation was blocked when lymphoblasts were pretreated with actin and tubulin cytoskeleton-interfering agents, indicating its cytoskeletal dependence. Our results demonstrate that interaction of the ␤2-integrin LFA-1 with its ligand intercellular adhesion molecule 1 induces remodeling of T lymphocyte morphology and activation and redistribution of the cytoplasmic tyrosine kinases FAK and PYK-2. INTRODUCTIONIntegrins are heterodimeric cell surface proteins that function in cell adhesion, cytoskeleton anchorage, and the transduction of cellular stimuli into cytoplasmic signals (Clark and Brugge, 1995;Schwartz et al., 1995).The ␤2-integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is selectively expressed on leukocytes and mediates important adhesive phenomena of these cells through interaction with its ligands intercellular adhesion molecule 1 (ICAM-1; CD54), ICAM-2 (CD102), and ICAM-3 (CD50). The resting leukocytes, which circulate in the bloodstream, express an inactive form of LFA-1 that is functionally unable to mediate interactions with ICAMs. Induction § Corresponding author. E-mail address: cacabagu@eucmax. sim.ucm.es.© 1999 by The American Society for Cell Biology 1891 of leukocyte activation through different cell surface receptors, including the T cell receptor-CD3 complex and receptors for cytokines, results in the generation of intracellular signals that lead to activation of LFA-1 molecules. This "inside-out" mechanism of LFA-1 activation brings about a change in the conformation of the extracellular region of the integrin, which is functionally reflected by the ability of the cells to adhere to LFA-1 ligands. Activation of LFA-1 molecules can also be induced directly from outside the cells by altering the extracellular divalent cation conditions, i.e. by addition of micromolar conc...

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Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Cited by 211 publications

References 41 publications

Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells

Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells

Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

The Interaction of Activated Integrin Lymphocyte Function-associated Antigen 1 with Ligand Intercellular Adhesion Molecule 1 Induces Activation and Redistribution of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 in T Lymphocytes

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