Roles of fascin in cell adhesion and motility.
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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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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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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ABSTRACT: Cancer cells that leave the primary tumor can seed metastases in distant organs, and it is thought that this is a unidirectional process. Here we show that circulating tumor cells (CTCs) can also colonize their tumors of origin, in a process that we call "tumor self-seeding." Self-seeding of breast cancer, colon cancer, and melanoma tumors in mice is preferentially mediated by aggressive CTCs, including those with bone, lung, or brain-metastatic tropism. We find that the tumor-derived cytokines IL-6 and IL-8 act as CTC attractants whereas MMP1/collagenase-1 and the actin cytoskeleton component fascin-1 are mediators of CTC infiltration into mammary tumors. We show that self-seeding can accelerate tumor growth, angiogenesis, and stromal recruitment through seed-derived factors including the chemokine CXCL1. Tumor self-seeding could explain the relationships between anaplasia, tumor size, vascularity and prognosis, and local recurrence seeded by disseminated cells following ostensibly complete tumor excision.Cell 12/2009; 139(7):1315-26. DOI:10.1016/j.cell.2009.11.025 · 33.12 Impact Factor