Expression of fascin in thyroid neoplasms: a novel diagnostic marker

Chen, Guang; Zhang, Fa-Ren; Ren, Jing; Tao, Lihua; Shen, Zhong-Ying; Lv, Zhuo; Yu, Shijiang; Dong, Bingfei; Xu, Li‐Yan; Li, En‐Min

doi:10.1007/s00432-008-0374-6

Cited by 22 publications

(23 citation statements)

References 20 publications

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“…For instance, studies conducted on ovarian epithelial tumors reveal increased fascin expression in advanced serous carcinomas as well as metastatic foci, associating fascin with increased tumor aggressiveness and suggesting it as candidate biomarker in gynecologic malignancies (24). In addition, fascin has also been reported to have significant diagnostic potential for thyroid neoplasms because it was shown to be highly upregulated in a number of thyroid carcinomas and adenomas (25). Furthermore, a recent tissue microarray -based immunohistochemical (IHC) study in breast tumors with basal-like phenotype described the overexpression of fascin coinciding with the up-regulation of markers related to epithelialmesenchymal transition, a phenomenon often associated with increased metastatic and invasive potential (26).…”

Section: Discussionmentioning

confidence: 99%

Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer

Darnel

Behmoaram

Vollmer

et al. 2009

Clinical Cancer Research

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Purpose: Prostate cancer metastasis to secondary organs is considered an initial event in the development of hormone refractory disease and remains the major cause of death among prostate cancer patients. In this study, we investigated the role of fascin, a cytoskeleton actinb undling protein involved in the formation of filopodia and cell migration, in prostate cancer progression. Experimental Design: Fascin protein expression was examined by immunohistochemistry in a cohort of 196 patients with localized prostate cancer and across several stages of disease progression, including hormone refractory disease. Cellular changes were also assessed in vitro and in vivo in DU145 prostate cancer cell line using fascin gene silencing. Results: Fascin epithelial expression was significantly up-regulated in localized and hormone refractory prostate cancer compared with benign prostate tissue (P < 0.05). Furthermore, high fascin expression was associated with an increased rate of prostate-specific antigen recurrence following radical prostatectomy (P = 0.075), signifying more aggressive clinical course, thus supporting a function for fascin in prostate cancer progression. In cellular models, fascin gene silencing using small interfering RNA in the androgen-independent prostate cancer cell line DU145 decreased cell motility and invasiveness while increasing cell adhesive properties. In addition, fascin small interfering RNA^expressing DU145 cells implanted orthotopically in mouse prostate showed significantly decreased growth (P < 0.005) and drastically prevented the formation of lymph node metastases (P < 0.001) compared with their matched controls. Conclusions:Our data show a function of fascin in the regulation of prostate cancer progression and emphasize the importance of fascin as a prognostic marker for aggressive disease and as a potential therapeutic target for advanced androgen independent disease.Prostate cancer remains one of the most prevalent cancers and a major source for morbidity and mortality in the Western world (1 -4). In 2007, f219,000 new patients were diagnosed with prostate cancer causing about 27,000 cancer related deaths (5). Disease progression and the development of hormone refractory disease remain major causes of cancer related death.To significantly alter the disease course, improved ways to understand, diagnose, and treat aggressive forms of metastatic prostate cancer are needed.Tumor cell motility is the hallmark of invasion and an essential step in metastasis (6, 7). Understanding the molecular pathways involved in tumor cell motility and how the tumor microenvironment contributes to cell migration and metastasis is critical to developing improved therapeutic targets for the treatment of metastatic prostate cancer. Predicting disease progression is a major and significant step in identifying patients at increased risk for cancer specific death. Therefore, one goal in the diagnosis and treatment of men with prostate cancer is to develop tissue-based molecular tests to distinguish ind...

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Section: Discussionmentioning

confidence: 99%

Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer

Darnel

Behmoaram

Vollmer

et al. 2009

Clinical Cancer Research

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“…Fascin is a cytoplasmic protein functioning to form the parallel actin bundles that support the lamellipodial and filopodial cell protrusions, which are key cellular structures for environmental guidance and cell migration [5,6]. The overexpression of fascin has been reported in various human carcinomas examined to date [7][8][9][10][11][12][13][14][15]. High expression levels of fascin in various primary carcinomas were consistently shown to correlate with aggressive tumor phenotypes and poor prognosis [7][8][9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation

et al. 2010

Cell. Mol. Life Sci.

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The overexpression of fascin in human carcinomas is associated with aggressive clinical phenotypes and poor prognosis. However, the molecular mechanism underlying the increased expression of fascin in cancer cells is largely unknown. Here, we identified a Sp1 binding element located at -70 to -60 nts of the FSCN1 promoter and validated that Sp1 specifically bound to this element in esophageal carcinoma cells. Fascin expression was enhanced by Sp1 overexpression and blocked by Sp1 RNAi knockdown. Specific inhibition of ERK1/2 decreased phosphorylation levels of Sp1, and thus suppressed the transcription of the FSCN1, resulting in the down-regulation of fascin. Stimulation with EGF could enhance fascin expression via activating the ERK1/2 pathway and increasing phosphorylation levels of Sp1. These data suggest that FSCN1 transcription may be subjected to the regulation of the EGF/EGFR signaling pathway and can be used as a viable biomarker to predict the efficacy of EGFR inhibitors in cancer therapies.

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“…It was named fascin because of its ability to form tight and stable bundles with F-actin (Kureishy et al 2002). Fascin is absent or shows very low expression in normal epithelium but is upregulated in transformed cells and in many kinds of human neoplasms, such as esophageal (Hashimoto et al 2005;Xue et al 2006), gastric (Hashimoto et al 2004), colonic (Hashimoto et al 2006), pancreatic (Yamaguchi et al 2007), lung (Pelosi et al 2003), breast (Rodríguez-Pinilla et al 2006), ovarian (Daponte et al 2008), prostate (Darnel et al 2009), and thyroid (Chen et al 2008) tumors, and high expression of fascin is associated with poor survival of patients.…”

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confidence: 99%

Phosphorylation of Fascin Decreases the Risk of Poor Survival in Patients With Esophageal Squamous Cell Carcinoma

Zhao

Shen

et al. 2010

J Histochem Cytochem.

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S U M M A R Y Phosphorylation of fascin at serine 39 (phospho-S39-fascin) could inhibit its actin-binding and actin-bundling activities and decrease filopodia formation. However, the relationship between phospho-S39-fascin expression and clinicopathological parameters in tumors is still unknown. Here, Western blot analysis and IHC applied to tissue microarray technology were performed to examine the expression status of non-phosphorylated fascin (fascin) and phospho-S39-fascin and their impacts on the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Fascin and phospho-S39-fascin expressions were tested by cytoplasmic staining. Among the 254 patients, 90 cases showed high expression of fascin and 87 cases showed high expression of phospho-S39-fascin. Survival analysis showed that high expression of fascin was significantly associated with a poor prognosis of the patients with ESCC (p50.004). In contrast, high expression of phospho-S39-fascin correlated significantly with an improved outcome of patients (p50.020). Multivariate analysis showed that both fascin and phospho-S39-fascin were independent prognostic factors. In a combined analysis, the patients with high expression of fascin and low expression of phospho-S39-fascin tumors had a shorter overall survival than those with high expression of both fascin and phospho-S39-fascin tumors (5-year overall survival rate: 28.7% vs 48.3%, p50.068). Our results suggest that high expression of fascin correlates with poor outcome and that high expression of phospho-S39-fascin decreases the risk of poor prognosis in ESCC. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. (J Histochem Cytochem 58:979-988, 2010)

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Expression of fascin in thyroid neoplasms: a novel diagnostic marker

Abstract: Fascin may be a novel marker to distinguish thyroid carcinoma from benign lesions and may be involved in the proliferation and metastasis of papillary carcinoma.

Cited by 22 publications

References 20 publications

Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer

Fascin Regulates Prostate Cancer Cell Invasion and Is Associated with Metastasis and Biochemical Failure in Prostate Cancer

Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation

Phosphorylation of Fascin Decreases the Risk of Poor Survival in Patients With Esophageal Squamous Cell Carcinoma

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