Changes in Adhesion Plaque Protein Levels Regulate Cell Motility And Tumorigenicity

Ben-Ze’ev, Avri; Fernández, José Luis Rodríguez; Glück, Ursula; Salomon, Daniela; Geiger, Benjamin

doi:10.1007/978-1-4615-2578-3_14

Cited by 14 publications

(11 citation statements)

References 32 publications

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“…Matrix adhesion is known to regulate the phosphorylation status of fascin and its association with F-actin 11 and it is likely that, under the assay conditions used, the cells contain both forms of fascin. A second obvious effect of fascin overexpression was on colony organization, both on a laminin substratum and within three-dimensional collagen gels.…”

Section: Discussionmentioning

confidence: 99%

“…8 Of these proteins, fascin is an actin cross-linking protein that localizes to the core actin bundles of spikes and filopodia at the leading edge of migratory cells and that has been implicated in cell motility in several cell types. 9,10 Although increased cell motility in cancer cells has been linked to decreased expression of several actin-associated proteins, including actinin and vinculin, 11 there are several reports that fascin expression is increased in certain cancers. Fascin expression is markedly increased in Epstein-Barr virus-transformed B lymphocytes and in the Reed-Sternberg cells of Hodgkin's lymphoma.…”

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confidence: 99%

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Fascin, an Actin-Bundling Protein, Modulates Colonic Epithelial Cell Invasiveness and Differentiation in Vitro

Jawhari¹,

Buda²,

Jenkins³

et al. 2003

The American Journal of Pathology

180

191

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In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility. We demonstrate that fascin is not detectable in normal colonic epithelium, but is dramatically up-regulated in colorectal adenocarcinoma. To test the hypothesis that fascin could participate in tumor invasive behavior, we developed a cell culture model to examine the effect of fascin expression on the adhesive interactions, invasiveness, and differentiation of colonic epithelial cells. We report marked effects on the organization of cell-surface protrusions, actin cytoskeleton, and focal adhesions in the absence of alterations in the protein levels of the major components of these structures. These effects correlate with alterations in cell movements on two-dimensional matrix, and increased invasiveness in three-dimensional matrix. The cells also show increased proliferation and decreased capacity for normal glandular differentiation in collagen gels. We propose that up-regulation of fascin, by promoting the formation of protrusive, actin-based, cell-motility structures, could be a significant component in the acquisition of invasive phe- Epithelial cell differentiation is fundamentally influenced by cell-matrix and cell-cell interactions. [1][2][3] In colonic epithelial cells, both the integrin and cadherin superfamilies of adhesion molecules are important contributors to the establishment of cell polarity and epithelial cell differentiation, and have been shown to play a role in the control of colorectal differentiation in tumor cells. 4,5 This is partly achieved through the formation of intracellular protein assemblies that anchor cytoskeletal actin filaments at defined areas within the cell membrane. In epithelial cells, these zones correspond to integrin-dependent focal adhesions and cadherin-containing adherens junctions and desmosomes. 6 These assemblies also function as important links in the integration of multiple cell signaling pathways. 3 Cell-matrix and cell-cell adhesive interactions normally stabilize the epithelial cell layer and maintain the cells in a nonmigratory state. However, the malignant conversion of epithelial cells involves a phenotypic switch to a migratory state that enables tumor invasion beyond the basement membrane and metastasis. The process of cell migration is poorly understood in epithelial cells, but studies in many types of carcinoma cells have documented increased formation of cell protrusions at cell margins, release of cell-cell contacts, and group movement of sheets of cells. In the models of cell motility that have been developed from studies of fibroblasts, protru...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fascin, an Actin-Bundling Protein, Modulates Colonic Epithelial Cell Invasiveness and Differentiation in Vitro

Jawhari¹,

Buda²,

Jenkins³

et al. 2003

The American Journal of Pathology

180

191

View full text Add to dashboard Cite

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“…The first described nonmuscle a-actinin, namely actinin-1, is primarily located in focal adhesion structures and participates in cadherin-mediated cell-cell adhesion via a-catenin at adherens junctions (Horwitz et al, 1986;Geiger et al, 1992;Fujimori and Takeichi, 1993;Otey et al, 1993;Knudsen et al, 1995). It has been reported that actinin-1 encoding gene (ACTN1) is able to suppress tumorigenicity and to regulate cell shape and cell motility Gluck et al, 1993;Ben-Ze'ev et al, 1994;Gluck and Ben-Ze'ev, 1994;Knudsen et al, 1995). Regarding the more recently identified nonmuscle a-actinin, a-actinin-4 (Honda et al, 1998), much less is known about its role in cytoskeletal organization and its precise biological function.…”

Section: Mutated Actn4 Affects Tumor Cell Migrationmentioning

confidence: 99%

“…Early studies of transformed cells showed a direct association between disorganization of the cytoskeleton and tumorigenicity or invasive capacity (Ben-Ze'ev, 1997). It has been shown that the expression of actin-associated proteins such as a-actinin-1 was decreased in cancer cells and that increased expression after cell transfection with cDNA encoding such proteins could reduce or abrogate metastatic potential (Gluck et al, 1993;Janmey and Chaponnier, 1995).…”

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confidence: 99%

Mutant α-actinin-4 promotes tumorigenicity and regulates cell motility of a human lung carcinoma

et al. 2004

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The precise role of a-actinin-4 encoding gene (ACTN4) is not very well understood. It has been reported to elicit tumor suppressor activity and to regulate cellular motility. To further assess the function of human ACTN4, we studied a lung carcinoma cell line expressing a mutated aactinin-4, which is recognized as a tumor antigen by autologous CD8 þ cytotoxic T lymphocytes (CTL). Confocal immunofluorescence microscopy indicated that, while wild-type (WT) a-actinin-4 stains into actin cytoskeleton and cell surface ruffles, the mutated protein is only dispersed in the cytoplasm of the lung carcinoma cells. This loss of association with the cell surface did not appear to correlate with a decrease in in vitro a-actinin-4 crosslinking to filamentous (F)-actin. Interestingly, experiments using cell lines stably expressing ACTN4 demonstrated that as opposed to WT gene, mutant ACTN4 was unable to inhibit tumor cell growth in vitro and in vivo. Moreover, the expression of mutant a-actinin-4 resulted in the loss of tumor cell capacity to migrate. The identification of an inactivating mutation in ACTN4 emphasizes its role as a tumor suppressor gene and underlines the involvement of cytoskeleton alteration in tumor development and metastasis.

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“…Moreover, a-actinin and vinculin, integrin-binding proteins with actin filaments, were found at sites of F-actin concentration. It has been reported that the expression of these proteins may affect the ability of cells to migrate [52][53][54].…”

Section: Discussionmentioning

confidence: 99%

Interaction of PC-3 cells with fibronectin adsorbed on sulfonated polystyrene surfaces

Stachurska

Kowalczyńska²

2012

Folia Histochem Cytobiol.

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Abstract:The ability of cancer cells to invade neighboring tissues is crucial for cell dissemination and tumor metastasis. It is generally assumed that cell adhesion to extracellular matrix proteins is an important stage of cancer progression. Hence, adhesion of cancer cells under in vitro conditions to proteins adsorbed on a substratum surface has been studied to provide a better understanding of cell-protein interaction mechanisms. A protein, adsorbed in an appropriate conformation on a substratum surface, creates a biologically active layer that regulates such cell functions as adhesion, spreading, proliferation and migration. In our study, we examined the interaction of PC-3 cells under in vitro conditions with fibronectin adsorbed on sulfonated polystyrene surfaces of a defined chemical composition and topography. We investigated cell adhesion to fibronectin and cell spreading. Using automatic, sequential microscopic image registration, we are the first to present observations of the dynamics of PC-3 cell spreading and the cell shape during this process. Our results show that cell adhesion and the shape of spreading cells strongly depend on the time interaction with fibronectin. The analysis of images of cytoskeletal protein distribution in the cell region near the cell-substratum interface revealed that induction of a signal cascade took place, which led to the reorganization of the cytoskeletal proteins and the activation of focal adhesion kinase (FAK).

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Changes in Adhesion Plaque Protein Levels Regulate Cell Motility And Tumorigenicity

Cited by 14 publications

References 32 publications

Fascin, an Actin-Bundling Protein, Modulates Colonic Epithelial Cell Invasiveness and Differentiation in Vitro

Fascin, an Actin-Bundling Protein, Modulates Colonic Epithelial Cell Invasiveness and Differentiation in Vitro

Mutant α-actinin-4 promotes tumorigenicity and regulates cell motility of a human lung carcinoma

Interaction of PC-3 cells with fibronectin adsorbed on sulfonated polystyrene surfaces

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