Alternative titles; symbols
HGNC Approved Gene Symbol: FSCN1
Cytogenetic location: 7p22.1 Genomic coordinates (GRCh38) : 7:5,592,816-5,606,655 (from NCBI)
Sea urchin fascin, one of the first actin-bundling proteins extensively characterized, can crosslink actin filaments in vitro (Bryan and Kane, 1982). The cloning of a fascin cDNA by Bryan et al. (1993) showed that fascin is homologous to the Drosophila singed gene product. Duh et al. (1994) isolated cDNAs encoding the human homolog of sea urchin fascin and Drosophila singed, called HSN by them, from a human teratocarcinoma cDNA library. The HSN mRNA was expressed at various levels in all human tissues analyzed and at high levels in actively growing renal carcinoma cell lines and in activated but not in resting lymphocytes, suggesting a functional role for HSN in proliferation. The HSN gene is predicted to encode a 493-amino acid protein with a molecular mass of 55 kD. Based on peptide sequence identity and immunocrossreactivity, Duh et al. (1994) indicated that the HSN protein is the 55-kD actin-bundling protein purified from HeLa cells (Yamashiro-Matsumura and Matsumura, 1985).
Yamashiro-Matsumura and Matsumura (1986) suggested that the 55-kD HSN protein is involved in the assembly of actin filament bundles present in microspikes, membrane ruffles, and stress fibers.
Yamakita et al. (1996) demonstrated that the actin-binding and -bundling activities of SNL are inhibited by phosphorylation. SNL is phosphorylated in vivo upon treatment with 12-O-tetradecanoylphorbol-13-acetate, a tumor promoter. The phosphorylation gradually increases, concomitant with the disappearance of SNL from stress fibers, microspikes, and membrane ruffles. Ono et al. (1997) identified serine-39 as the major site of SNL phosphorylation. This site is highly conserved among all fascin homologs. Substitution of serine-39 with alanine eliminated the phosphorylation-dependent regulation of the actin-binding activity of SNL, indicating that phosphorylation at this site regulates the actin-binding ability of SNL. Ono et al. (1997) found that the C-terminal half of SNL contains an actin-binding domain.
Using immunofluorescence microscopy and Western blot analysis, Mosialos et al. (1996) demonstrated that an anti-p55 antibody reacted with nearly all purified dendritic cells but not with other blood leukocytes. Expression of p55 colocalized with actin. Immunohistochemistry indicated that p55 is expressed in dendritic cells in lymph node T-cell zones.
Sonderbye et al. (1997) used flow cytometric and immunohistochemical analyses to show that expression of fascin is rare in CD34 (142230)-positive progenitor cells but that cytoplasmic expression increases with differentiation in culture until nearly all dendritic cells are fascin-positive.
Using immunohistochemistry, Pinkus et al. (1997) found that nearly all Reed-Sternberg cells in Hodgkin disease (236000), except in the nodular lymphocyte predominance type, express fascin. They proposed that fascin expression may be helpful in distinguishing Hodgkin from non-Hodgkin lymphoma and suggested that Reed-Sternberg cells may have a dendritic cell derivation.
By in vivo selection, transcriptomic analysis, functional verification, and clinical validation, Minn et al. (2005) identified a set of genes that marks and mediates breast cancer metastasis to the lungs. Some of these genes serve dual functions, providing growth advantages both in the primary tumor and in the lung microenvironment. Others contribute to aggressive growth selectivity in the lung. Two that were not functionally validated but that achieved the highest statistical significance (P less than 0.000001) were FSCN1 and angiopoietin-like-4 (ANGPTL4; 605910). Those subjects expressing the lung metastasis signature had a significantly poorer lung metastasis-free survival, but not bone metastasis-free survival, compared to subjects without the signature.
Zhang et al. (2009) found that RAB35 (604199) regulates the assembly of actin filaments during bristle development in Drosophila and filopodia formation in cultured cells. These effects were mediated by the actin-bundling protein fascin, which directly associated with active Rab35. Targeting Rab35 to the outer mitochondrial membrane triggered actin recruitment, demonstrating a role for an intracellular trafficking protein in localized actin assembly.
Duh et al. (1994) mapped the SNL gene to 7p22 by fluorescence in situ hybridization.
Bryan, J., Edwards, R., Matsudaira, P., Otto, J., Wulfkuhle, J. Fascin, an echinoid actin-bundling protein, is a homolog of the Drosophila singed gene product. Proc. Nat. Acad. Sci. 90: 9115-9119, 1993. [PubMed: 8415664] [Full Text: https://doi.org/10.1073/pnas.90.19.9115]
Bryan, J., Kane, R. E. Actin gelation in sea urchin egg extracts. Methods Cell Biol. 25: 175-199, 1982. [PubMed: 7202107] [Full Text: https://doi.org/10.1016/s0091-679x(08)61425-9]
Duh, F.-M., Latif, F., Weng, Y., Geil, L., Modi, W., Stackhouse, T., Matsumura, F., Duan, D. R., Linehan, W. M., Lerman, M. I., Gnarra, J. R. cDNA cloning and expression of the human homolog of the sea urchin fascin and Drosophila singed genes which encodes an actin-bundling protein. DNA Cell Biol. 13: 821-827, 1994. [PubMed: 8068206] [Full Text: https://doi.org/10.1089/dna.1994.13.821]
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., Massague, J. Genes that mediate breast cancer metastasis to lung. Nature 436: 518-524, 2005. [PubMed: 16049480] [Full Text: https://doi.org/10.1038/nature03799]
Mosialos, G., Birkenbach, M., Ayehunie, S., Matsumura, F., Pinkus, G. S., Kieff, E., Langhoff, E. Circulating human dendritic cells differentially express high levels of a 55-kD actin-bundling protein. Am. J. Path. 148: 593-600, 1996. [PubMed: 8579121]
Ono, S., Yamakita, Y., Yamashiro, S., Matsudaira, P. T., Gnarra, J. R., Obinata, T., Matsumura, F. Identification of an actin binding region and a protein kinase C phosphorylation site on human fascin. J. Biol. Chem. 272: 2527-2533, 1997. [PubMed: 8999969] [Full Text: https://doi.org/10.1074/jbc.272.4.2527]
Pinkus, G. S., Pinkus, J. L., Langhoff, E., Matsumura, F., Yamashiro, S., Mosialos, G., Said, J. W. Fascin, a sensitive new marker for Reed-Sternberg cells of Hodgkin's disease: evidence for a dendritic or B cell derivation? Am. J. Path. 150: 543-562, 1997. [PubMed: 9033270]
Sonderbye, L., Magerstadt, R., Blatman, R. N., Preffer, F. I., Langhoff, E. Selective expression of human fascin (p55) by dendritic leukocytes. Adv. Exp. Med. Biol. 471: 41-46, 1997.
Yamakita, Y., Ono, S., Matsumura, F., Yamashiro, S. Phosphorylation of human fascin inhibits its actin binding and bundling activities. J. Biol. Chem. 271: 12632-12638, 1996. [PubMed: 8647875] [Full Text: https://doi.org/10.1074/jbc.271.21.12632]
Yamashiro-Matsumura, S., Matsumura, F. Intracellular localization of the 55-kD actin-bundling protein in cultured cells: spatial relationships with actin, alpha-actinin, tropomyosin, and fimbrin. J. Cell Biol. 103: 631-640, 1986. [PubMed: 3525578] [Full Text: https://doi.org/10.1083/jcb.103.2.631]
Yamashiro-Matsumura, S., Matsumura, F. Purification and characterization of an F-actin-bundling 55-kilodalton protein from HeLa cells. J. Biol. Chem. 260: 5087-5097, 1985. [PubMed: 3886649]
Zhang, J., Fonovic, M., Suyama, K., Bogyo, M., Scott, M. P. Rab35 controls actin bundling by recruiting fascin as an effector protein. Science 325: 1250-1254, 2009. [PubMed: 19729655] [Full Text: https://doi.org/10.1126/science.1174921]