Roles of fascin in cell adhesion and motility

Dept of Cell Biology, NC1-110, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Current Opinion in Cell Biology (Impact Factor: 8.74). 11/2004; 16(5):590-6. DOI: 10.1016/
Source: PubMed

ABSTRACT Many cell interactions depend on the assembly of cell protrusions; these include cell attachment and migration in the extracellular matrix, cell-cell communication, and the ability of cells to sense their local environment. Cell protrusions are extensions of the plasma membrane that are supported internally by actin-based structures that impart mechanical stiffness. Fascin is a small, globular actin-bundling protein that has emerging roles in diverse forms of cell protrusions and in cytoplasmic actin bundles. The fascin-actin interaction is under complex regulation from the extracellular matrix, peptide factors and other actin-binding proteins. Recent developments advance our understanding of the multifaceted regulation of fascin and the roles of fascin-containing structures in cell adhesion, motility and invasion in the life of vertebrate organisms.

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    • "Because bridges were similar in structure and filament polarity to traditional filopodia, we tested whether bridges share other key features with filopodia. First, we determined the localization of a bundling protein fascin, which is considered to be a key marker of filopodia (Svitkina et al., 2003; Adams, 2004; Vignjevic et al., 2006; Lee et al., 2010). Consistent with the filopodia-like morphology of bridges, immunostaining of fascin revealed its localization to bridges (Figure 3B). "
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    ABSTRACT: The actin cytoskeleton and associated proteins play a vital role in cell-cell adhesion. However, the procedure by which cells establish adherens junctions remains unclear. We investigated the dynamics of cell-cell junction formation and the corresponding architecture of the underlying cytoskeleton in cultured human umbilical vein endothelial cells. We show that the initial interaction between cells is mediated by protruding lamellipodia. On their retraction, cells maintain contact through thin bridges formed by filopodia-like protrusions connected by VE-cadherin-rich junctions. Bridges share multiple features with conventional filopodia, such as an internal actin bundle associated with fascin along the length and vasodilator-stimulated phosphoprotein at the tip. It is striking that, unlike conventional filopodia, transformation of actin organization from the lamellipodial network to filopodial bundle during bridge formation occurs in a proximal-to-distal direction and is accompanied by recruitment of fascin in the same direction. Subsequently, bridge bundles recruit nonmuscle myosin II and mature into stress fibers. Myosin II activity is important for bridge formation and accumulation of VE-cadherin in nascent adherens junctions. Our data reveal a mechanism of cell-cell junction formation in endothelial cells using lamellipodia as the initial protrusive contact, subsequently transforming into filopodia-like bridges connected through adherens junctions. Moreover, a novel lamellipodia-to-filopodia transition is used in this context.
    Molecular biology of the cell 11/2011; 23(2):310-23. DOI:10.1091/mbc.E11-08-0719 · 5.98 Impact Factor
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    • "Our proteomics analysis revealed that K8 depletion led to reduction in the levels of the cell-motility-associated protein fascin (Fig. 3A,B). Fascin is a globular actin cross-linking protein that is widely expressed in mesenchymal and neuronal cells and is low or absent in adult epithelia (Adams, 2004; Yamashiro et al., 1998). It is upregulated in many human carcinomas, including OSCC, and an increased level of fascin correlates with the clinical aggressiveness of tumours and poor patient survival (Hashimoto et al., 2005). "
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    ABSTRACT: Keratins 8 and 18 (K8 and K18) are predominantly expressed in simple epithelial tissues and perform both mechanical and regulatory functions. Aberrant expression of K8 and K18 is associated with neoplastic progression and invasion in squamous cell carcinomas (SCCs). To understand the molecular basis by which K8 promotes neoplastic progression in oral SCC (OSCC), K8 expression was inhibited in AW13516 cells. The K8-knockdown clones showed a significant reduction in tumorigenic potential, which was accompanied by a reduction in cell motility, cell invasion, decreased fascin levels, alterations in the organization of the actin cytoskeleton and changes in cell shape. Furthermore, K8 knockdown led to a decrease in α6β4 integrin levels and α6β4-integrin-dependent signalling events, which have been reported to play an important role in neoplastic progression in epithelial tissues. Therefore, modulation of α6β4 integrin signalling might be one of the mechanisms by which K8 and K18 promote malignant transformation and/or progression in OSCCs.
    Journal of Cell Science 06/2011; 124(Pt 12):2096-106. DOI:10.1242/jcs.073585 · 5.33 Impact Factor
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    • "Fascin has been widely shown to regulate assembly of actin bundles in a variety of different cellular contexts (reviewed in Adams, 2004). "
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    ABSTRACT: Fascin is a 55 kDa actin-bundling protein and is an important regulatory element in the maintenance and stability of parallel bundles of filamentous actin in a variety of cellular contexts. Regulation of fascin function is under the control of a number of different signalling pathways that act in concert to spatially regulate the actin-binding properties of this protein. The ability of fascin to bind and bundle actin plays a central role in the regulation of cell adhesion, migration and invasion. Fascin has received considerable attention recently as an emerging key prognostic marker of metastatic disease. Studies are now underway to better understand the precise regulation of this protein in the context of tumour progression and to investigate fascin as a potential therapeutic target for a number of forms of cancer.
    The international journal of biochemistry & cell biology 10/2010; 42(10):1614-7. DOI:10.1016/j.biocel.2010.06.019 · 4.24 Impact Factor
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