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: 8.47). 11/2004; 16(5):590-6. DOI: 10.1016/
Source: PubMed


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.

1 Follower
16 Reads
    • "Fascin is a highly conserved actin-bundling protein with three isoforms: while Fascin-1 is nearly ubiquitously expressed during embryogenesis, its expression is later restricted to endothelium, neuronal tissue, and testis [11]. Fascin-2 and Fascin-3, respectively, are expressed in retinal epithelium and testis only [34]. Fascin is phosphorylated by protein kinase C (PKC), which regulates its actinbundling activity dependent on current microenvironmental conditions which are communicated via surface integrins [11]; however, increased expression levels of Fascin have been described in several gastrointestinal malignancies as well as in invasive breast cancer and malignant melanoma. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Reorganization of the actin cytoskeleton underlies cell migration in a wide variety of physiological and pathological processes, such as embryonic development, wound healing, and tumor cell invasion. It has been shown that actin assembly and disassembly are precisely regulated by intracellular signaling cascades that respond to changes in the cell microenvironment, ligand binding to surface receptors, or oncogenic transformation of the cell. Actin-nucleating and actin-depolymerizing (ANFs/ADFs) and nucleation-promoting factors (NPFs) regulate cytoskeletal dynamics at the leading edge of migrating cells, therebymodulating cell shape; these proteins facilitate cellular movement and mediate degradation of the surrounding extracellular matrix by secretion of lytic proteases, thus eliminating barriers for tumor cell invasion. Accordingly, expression and activity of these actin-binding proteins have been linked to enhanced metastasis and poor prognosis in a variety of malignancies. In this review, we will summarize what is known about expression patterns and the functional role of actin regulators in gastrointestinal tumors and evaluate first pharmacological approaches to prevent invasion and metastatic dissemination of malignant cells.
    Gastroenterology Research and Practice 07/2015; 2015(3). DOI:10.1155/2015/930157 · 1.75 Impact Factor
  • Source
    • "These molecules are the downstream signaling proteins in the signaling pathways that regulate the invasive or structural actin cytoskeleton. Among these proteins, fascin, which binds to the filaments in filopodia, plays a key role in establishing these filaments, whose over-expression generally induces greater filopodial growth [5]–[8]. Arp2/3, which is usually found in lamellipodia, acts as a nucleation core for the assembly of new branch filaments, through which the complex stimulates filament polymerization in the cell leading edge [4], [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In this article, we have examined the motility-related effects of weak power frequency magnetic fields (MFs) on the epidermal growth factor receptor (EGFR)-sensitive motility mechanism, including the F-actin cytoskeleton, growth of invasive protrusions and the levels of signal molecules in human amniotic epithelial (FL) cells. Without extracellular EGF stimulation, the field stimulated a large growth of new protrusions, especially filopodia and lamellipodia, an increased population of vinculin-associated focal adhesions. And, an obvious reduction of stress fiber content in cell centers was found, corresponding to larger cell surface areas and decreased efficiency of actin assembly of FL cells in vitro, which was associated with a decrease in overall F-actin content and special distributions. These effects were also associated with changes in protein content or distribution patterns of the EGFR downstream motility-related signaling molecules. All of these effects are similar to those following epidermal growth factor (EGF) stimulation of the cells and are time dependent. These results suggest that power frequency MF exposure acutely affects the migration/motility-related actin cytoskeleton reorganization that is regulated by the EGFR-cytoskeleton signaling pathway. Therefore, upon the MF exposure, cells are likely altered to be ready to transfer into a state of migration in response to the stimuli.
    PLoS ONE 02/2014; 9(2):e87626. DOI:10.1371/journal.pone.0087626 · 3.23 Impact Factor
  • Source
    • "Fibronectin-mediated activation of PKCα inhibits the formation of nascent adhesions and cell protrusions by phosphorylating fascin (at Ser 39 ) to block its association with actin and thereby its functioning in F-actin polymerization (Adams 2004). A dynamic activity of PKCα is probably required in this context. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cell adhesion to extracellular matrix is a complex process involving protrusive activity driven by the actin cytoskeleton, engagement of specific receptors, followed by signaling and cytoskeletal organization. Thereafter, contractile and endocytic/recycling activities may facilitate migration and adhesion turnover. Focal adhesions, or focal contacts, are widespread organelles at the cell-matrix interface. They arise as a result of receptor interactions with matrix ligands, together with clustering. Recent analysis shows that focal adhesions contain a very large number of protein components in their intracellular compartment. Among these are tyrosine kinases, which have received a great deal of attention, whereas the serine/threonine kinase protein kinase C has received much less. Here the status of protein kinase C in focal adhesions and cell migration is reviewed, together with discussion of its roles and potential substrates.
    Journal of Histochemistry and Cytochemistry 12/2013; 62(3). DOI:10.1369/0022155413517701 · 1.96 Impact Factor
Show more