Fascin Expression in Human Embryonic, Fetal, and Normal Adult Tissue

Zhang, Fa-Ren; Tao, Lihua; Shen, Zhong-Ying; Lv, Zhuo; Xu, Li‐Yan; Li, En‐Min

doi:10.1369/jhc.7a7353.2007

Cited by 97 publications

(95 citation statements)

References 27 publications

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“…The cases were received between 1987 and 1997. The cases were selected to build tissue microarrays as described (28) and were included in this study only if a follow-up was obtained and clinical data were available. Mean age at surgery was 53 years (range , and 127 patients were male and 66 were female.…”

Section: Methodsmentioning

confidence: 99%

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Gao

Cui

et al. 2009

Journal of Biological Chemistry

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Ezrin, encoded by VIL2, is a membrane-cytoskeletal linker protein that has been suggested to be involved in tumorigenesis. Ezrin expression in esophageal squamous cell carcinoma (ESCC) was described recently, but its clinical significance and the molecular mechanism underlying its regulated expression remain unclear. Thus, we retrospectively evaluated ezrin expression by immunohistochemistry in a tissue microarray representing 193 ESCCs. Ezrin overexpression in 90 of 193 tumors (46.6%) was associated with poor survival (p ‫؍‬ 0.048). We then explored the mechanism by which ezrin expression is controlled in ESCC by assessing the transcriptional regulatory regions of human VIL2 by fusing deletions or site-directed mutants of the 5-flanking region of the gene to a luciferase reporter. We found that the region ؊87/؊32 containing consensus Sp1 (؊75/؊69) and AP-1 (؊64/؊58) binding sites is crucial for VIL2 promoter activity in esophageal carcinoma cells

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Section: Methodsmentioning

confidence: 99%

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Gao

Cui

et al. 2009

Journal of Biological Chemistry

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“…By contrast, it has been reported that fascin + tumor epithelium has strong invasiveness with poorer prognosis in various carcinomas, such as ovarian, breast, pancreas, lung, cutaneous, brain, gastrointestinal, thyroid, prostate, urothelial, intrahepatic cholangiocarcinoma and skin tumors (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The significance of epithelial fascin expression has been reported to be associated with invasiveness and metastasis, since it aids in cell migration and proliferation through increases in lamellipodial and filopodial cell protrusions (15).…”

Section: Epithelium -------------------------------------------------mentioning

confidence: 99%

“…In normal adult human tissues, fascin expression is restricted to neurons and DCs; both cell types have markedly large filopodia and are highly motile (11,13). Fascin expression in various neoplastic cells has also been investigated, and its expression has been reported to be associated with epithelial to mesenchymal progression and invasion of tumor cells as well as a clinically aggressive manifestation and poorer prognosis (14)(15)(16)(17)(18)(19)(20)(21)(22)(23). However, to the best of our knowledge, immunohistochemical studies for the detection of fascin + mature DCs in thymoma have yet to be performed.…”

Section: Introductionmentioning

confidence: 99%

Fascin expression in dendritic cells and tumor epithelium in thymoma and thymic carcinoma

et al. 2011

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Abstract. The majority of thymomas are histologically characterized by tumor-infiltrating lymphocytes. Mature dendritic cells (DCs) are known to assemble lymphocytes through antigen presentation to T lymphocytes. Fascin, a 55-kDa actin-binding protein and a known marker for mature DCs, regulates filaments necessary for the formation of filopodia in cell migration. Moreover, fascin expression in various epithelial neoplasms has recently been reported to be associated with invasion of tumor cells and clinically aggressive manifestations. In the present study, we investigated fascin expression immunohistochemically in tissues of thymomas and thymic carcinomas surgically resected at our institute. A total of 34 thymomas and 5 thymic carcinomas were included. The amount and immunohistochemical intensity of both fascin + DCs and tumor epithelium were counted and assessed, and the clinicopathological data were also scored. Statistical analyses revealed that the amount of fascin + DCs with the formation of clusters was associated with lymphocyte-rich variants (p=0.002) and cortical differentiation (p=0.037) of thymoma with complication from myasthenia gravis (p=0.002). The quantity of fascin + epithelium was associated with a strong intensity of fascin in infiltrating DCs (p=0.002) with the formation of clusters (p=0.002) and favorable prognosis, as assessed by the Masaoka staging system (p=0.001). The amount of infiltrating DCs (p=0.024) and fascin + epithelium were lower in thymic carcinoma. It was concluded that fascin + epithelium may induce tumor immunity through the surveillance activity of fascin + DCs in thymic neoplasms, thus improving prognosis.

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“…Fascin-1 is abundant early in development, especially in the central nervous system (CNS) and migrating cells, and is then downregulated as cells mature (De Arcangelis et al, 2004;Zhang et al, 2008;Zanet et al, 2009;Tang et al, 2010). In this paper, 'fascin' refers to the product of the Fascin-1 genes (FSCN1 in humans, MIM#602689; Fscn1 in mouse; and singed in Drosophila, FBgn0003447).…”

Section: Introductionmentioning

confidence: 99%

A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

Kraft¹,

Kahn²,

Medina‐Franco³

et al. 2013

Journal of Cell Science

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SUMMARYThe actin-bundling protein fascin is a key mediator of tumor invasion and metastasis and its activity drives filopodia formation, cell-shape changes and cell migration. Small-molecule inhibitors of fascin block tumor metastasis in animal models. Conversely, fascin deficiency might underlie the pathogenesis of some developmental brain disorders. To identify fascin-pathway modulators we devised a cell-based assay for fascin function and used it in a bidirectional drug screen. The screen utilized cultured fascin-deficient mutant Drosophila neurons, whose neurite arbors manifest the 'filagree' phenotype. Taking a repurposing approach, we screened a library of 1040 known compounds, many of them FDA-approved drugs, for filagree modifiers. Based on scaffold distribution, molecular-fingerprint similarities, and chemical-space distribution, this library has high structural diversity, supporting its utility as a screening tool. We identified 34 fascin-pathway blockers (with potential anti-metastasis activity) and 48 fascinpathway enhancers (with potential cognitive-enhancer activity). The structural diversity of the active compounds suggests multiple molecular targets. Comparisons of active and inactive compounds provided preliminary structure-activity relationship information. The screen also revealed diverse neurotoxic effects of other drugs, notably the 'beads-on-a-string' defect, which is induced solely by statins. Statin-induced neurotoxicity is enhanced by fascin deficiency. In summary, we provide evidence that primary neuron culture using a genetic model organism can be valuable for early-stage drug discovery and developmental neurotoxicity testing. Furthermore, we propose that, given an appropriate assay for target-pathway function, bidirectional screening for brain-development disorders and invasive cancers represents an efficient, multipurpose strategy for drug discovery.

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Fascin Expression in Human Embryonic, Fetal, and Normal Adult Tissue

Cited by 97 publications

References 27 publications

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Sp1 and AP-1 Regulate Expression of the Human Gene VIL2 in Esophageal Carcinoma Cells

Fascin expression in dendritic cells and tumor epithelium in thymoma and thymic carcinoma

A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions

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