Disease relevance of FSCN1

• Our findings, along with the regulation of human Fascin1 (OMIM 602689) by CREB (cAMP response element-binding protein) binding protein, suggest FSCN1 as a candidate gene for developmental brain disorders [1].
• Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation [2]?
• This study was initiated to examine the differential expression of an evolutionary conserved human 55-kd actin-bundling (p55) protein that is induced in B lymphocytes by Epstein-Barr virus infection [3].
• Fascin represents a highly effective marker for detection of certain dendritic cells in normal and neoplastic tissues, is an extremely consistent marker for Reed-Sternberg cells and variants of Hodgkin's disease (except L&H types), and may be helpful to distinguish between Hodgkin's disease and non-Hodgkin's lymphoma in difficult cases [2].
• Fascin expression has been associated with lung metastasis in breast cancer [4].
• The activity of Rac on the fascin/PKC complex was mediated in part by Pak. Elucidation of this novel pathway for regulation of the fascin/PKCgamma complex in migrating carcinoma cells suggests novel targets for therapeutic intervention in metastasis [5].

High impact information on FSCN1

• Formation of filopodia in coelomocytes: localization of fascin, a 58,000 dalton actin cross-linking protein [6].
• Roles of fascin in cell adhesion and motility [7].
• We propose that fascin is a key specific actin cross-linker, providing stiffness for filopodial bundles, and that its dynamic behavior allows for efficient coordination between elongation and bundling of filopodial actin filaments [8].
• Analysis of cellular localization of known actin cross-linking proteins in mouse melanoma B16F1 cells revealed that fascin was specifically localized along the entire length of all filopodia, whereas other actin cross-linkers were not [8].
• RNA interference of fascin reduced the number of filopodia, and remaining filopodia had abnormal morphology with wavy and loosely bundled actin organization [8].

Chemical compound and disease context of FSCN1

• Several nonprimate cell lines (mink Mv-1-lu, rabbit SIRC, hamster a23, mouse NIH 3T3, cat CCC, and rat HSN) remained resistant to infection by LAV-2/B after treatment with glycosylation inhibitors, suggesting that they do not express the HIV-2 CD4-independent receptor [9].
• Uptake in hooded rat sarcoma (HSN) cells, which express Pgp, is significantly increased in the presence of the MDR modulator cyclosporin A [10].
• In this study, we prepared an ethanol extract from ripe fruits of SNL and investigated the mechanism involved in its growth-inhibitory effect on MCF-7 human breast cancer cells [11].
• Upregulation of alpha 1 beta 1 integrin on mesangial regions in biopsy specimens in patients with HSN may be connected to the much more florid glomerular changes in renal tissue in this type of glomerulonephritis than in IgAN [12].

Biological context of FSCN1

• Interaction of fascin and protein kinase Calpha: a novel intersection in cell adhesion and motility [13].
• To understand the mechanism of fascin-actin interactions, we dissected the actin binding region and its regulatory site by phosphorylation of human fascin [14].
• NG2- and fascin-positive structures are often localized to opposite poles of spreading cells, suggesting a possible role for the two classes of cellular extensions in the establishment of cell polarity during morphogenesis or migration [15].
• The human fascin gene promoter is highly active in mature dendritic cells due to a stage-specific enhancer [16].
• Although fascin expression was associated with the basal-like phenotype, it was not associated with their metastatic behavior [4].

Anatomical context of FSCN1

• We report an unexpected direct association between fascin, an actin-bundling component of filopodia, microspikes and lamellipodial ribs, and protein kinase Calpha (PKCalpha), a regulator of focal adhesions [13].
• In the peripheral blood, only dendritic (veiled) cells were reactive for fascin [2].
• Human fascin is an actin-bundling protein that is thought to be involved in the assembly of actin filament bundles present in microspikes as well as in membrane ruffles and stress fibers [17].
• Our study demonstrates that p55 is specifically expressed at constitutively high levels in human peripheral blood dendritic cells and lymph node (interdigitating) dendritic cells [3].
• The promoter exerted robust activity in DC and a fascin-positive neuronal cell line, but not in the fascin-negative cells tested [16].

Associations of FSCN1 with chemical compounds

• The lower amount of FSCN1 transcript in the absence of the CBP factor was also established in RA-treated cells [18].
• Cells treated with genistein also spread and formed fascin-containing microspikes which tended to be more slender than those of control cells [19].
• Indeed, although vanadate-treated cells tended to retract, the microspikes became more prominent and showed an increased intensity of staining for fascin [19].
• In contrast, cells adherent on fibronectin displayed a complex rearrangement of the actin cytoskeleton and a transient enrichment of 55 kDa/fascin-containing structures at the cell surface when treated with sodium orthovanadate and hydrogen peroxide [19].
• Both subcutaneous carbamazepine (0.5-22.5 mg/kg) and gabapentin (10-100 mg/kg) significantly reduced the spontaneous activity of spinal neurones of SNL rats at both PO time points [20].

Other interactions of FSCN1

• Minor expression of fascin-1 gene (FSCN1) in NTera2 cells depleted of CREB-binding protein [18].
• The sarcomatous component was diffusely positive for fascin, nerve growth factor receptor, and CD34 with focal weak reactivity for CD21 and CNA.42 [21].
• Here, we examined the structure of the actin bundle formed by human fascin-1 (actin/fascin bundle), and its mode of interaction with myosin in vitro [22].
• In the in vitro motility assay, actin/fascin bundles slid as fast as single actin filaments on myosin II and myosin V [22].
• Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021) [23].

Analytical, diagnostic and therapeutic context of FSCN1

• Hybridization experiments on 1.2K human cDNA microarrays showed that the FSCN1 gene, encoding for fascin-1 protein, was clearly less expressed in CBP-depleted cells than in controls [18].
• Western blot analysis confirmed that only the dendritic cell component of peripheral blood expressed high levels of p55 [3].
• Western blot and immunofluorescence analysis revealed cLC-specific expression of fascin on the protein level as well [24].
• These results suggest that phosphorylation of fascin plays a role in actin reorganization after treatment with 12-O-tetradecanoylphorbol-13-acetate [17].
• By competitive RT-PCR, we confirmed that fascin is highly expressed in cLC cultivated for 1, 2, and 3 days, while no signals were obtained with fLC [24].

References