Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

Xie, Jian‐Jun; Xu, Li‐Yan; Zhang, H.H.; Cai, Weijia; Mai, Rongjia; Xie, Yang‐Min; Yang, Zidong; Niu, Yongdong; Shen, Zhong-Ying; Li, E.M.

doi:10.1016/j.bbrc.2005.09.055

Cited by 95 publications

(110 citation statements)

References 32 publications

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“…Using RNA interference, it has been shown recently that down-regulation of fascin has inhibitory effects on the migration, proliferation and invasiveness of esophageal squamous cell carcinoma cell lines. 24,25 These data suggest that fascin itself contributes to tumor progression, and raise the possibility that fascin could be a novel therapeutic target.…”

Section: Discussionmentioning

confidence: 95%

“…In vitro experiments have indicated that it is involved in cellular processes such as motility, 27,38,39 loss of cell-cell contact in relation to adhesion molecules, [39][40][41] and cell proliferation. 25,27 From these observations, it may be presumed that fascin may play an important role in cellular malignant transformation. Indeed, in a variety of human carcinomas, fascin expression is consistently associated with the clinical aggressiveness of the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…It is required for the formation of actin-based cell-surface protrusions that are essential for cellular migration and cellmatrix adhesion. [15][16][17] In normal epithelial cells, fascin expression is usually absent or very low, but it is significantly upregulated in transformed epithelial cells and several types of human carcinoma such as lung, 18,19 breast, [20][21][22][23] esophagus, 24,25 stomach, 26 colon, 27 pancreas, [28][29][30][31] biliary tract and ampulla, 31,32 ovary, 33 urinary bladder, 34 and skin. 35 Among the above neoplasms, fascin upregulation is most frequently observed in pancreatic infiltrating adenocarcinoma.…”

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Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

et al. 2007

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Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms and a precursor of infiltrating adenocarcinoma. Fascin, an actin-bundling protein involved in cellular motility, is upregulated in many human neoplasms. Its overexpression in pancreatic intraepithelial neoplasia, a precancerous lesion sharing many characteristics with IPMN, has been reported. However, fascin expression in IPMN remains unknown. The aim of this study was to investigate fascin expression in IPMNs and to elucidate its relationship to clinicopathological features, including histological grade and phenotypic subclassification. We evaluated fascin expression by immunohistochemistry in 116 surgical specimens, followed by quantitative analysis of fascin mRNA expression using a laser microdissection system and real-time reverse-transcriptase polymerase chain reaction in eight frozen samples. Fascin expression was significantly higher in borderline neoplasms (25/29, 86%) and carcinomas (37/42, 88%) than in adenomas (23/45, 51%) (Po0.05, respectively), but no difference was observed between borderline neoplasms and carcinomas. With regard to the subclassification, intestinal-type neoplasms (35/39, 90%) were more frequently positive for fascin than gastric-type neoplasms (36/59, 61%) (Po0.05). Two oncocytic-type neoplasms were both fascin-negative. Fascin mRNA expression seemed to be higher in moderately to severely dysplastic epithelium than in mildly dysplastic epithelium (not statistically significant), supporting the immunohistochemical experiments. Our findings suggest that fascin overexpression is involved in the progression of IPMN. Keywords: intraductal papillary mucinous neoplasm; fascin; immunohistochemistry; laser microdissection; realtime RT-PCR; phenotypic subclassification Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity in pancreatic neoplasms. It was first reported in 1982 as a special type of pancreatic neoplasm with a characteristic endoscopic finding of extrusion of mucin through the ampulla of Vater. 1 At present, the term is used to unify tumors characterized by intraductal proliferation of neoplastic mucinous epithelium, which usually forms papillae and leads to cystic dilation of the pancreatic ducts. 2,3 Because IPMNs show a broad spectrum of dysplasia ranging from adenoma and borderline neoplasm to carcinoma in situ, the existence of an adenoma-carcinoma sequence is probable. In addition, some IPMNs are associated with infiltrating adenocarcinoma. Therefore, IPMN is gaining attention as a precursor of infiltrating adenocarcinoma in the pancreas as well as pancreatic intraepithelial neoplasia (PanIN). [4][5][6] Investigation of factors correlated with the progression of noninvasive and/or invasive IPMNs is important.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

et al. 2007

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“…The main results are that fascin is upregulated in most colonic carcinomas, correlating with a higher tumour grade, right tumour location and tumour stage, and that fascin immunoreactivity is an independent predictor of reduced OS and DFS in patients with advanced tumour stage. A growing body of literature reports that fascin is expressed in many types of transformed epithelial cell lines and in several solid neoplasms (Grothey et al, 2000;Hu et al, 2000;Goncharuk et al, 2002;Jawhari et al, 2003;Pelosi et al, 2003a, b;Hashimoto et al, 2004Hashimoto et al, , 2005aHashimoto et al, , 2006Tong et al, 2005;Xie et al, 2005;Yoder et al, 2005;Choi et al, 2006;Zhang et al, 2006) where it correlates with tumour stage (Hashimoto et al, 2004(Hashimoto et al, , 2005aYoder et al, 2005;Choi et al, 2006) and grade (Pelosi et al, 2003b;Hashimoto et al, 2004;Yoder et al, 2005), pT class (Hashimoto et al, 2004(Hashimoto et al, , 2005a, lymph node involvement (Hashimoto et al, 2004(Hashimoto et al, , 2005aChoi et al, 2006;Zhang et al, 2006), recurrence (Hashimoto et al, 2004), and both OS (Hashimoto et al, 2004(Hashimoto et al, , 2005a(Hashimoto et al, , 2006Yoder et al, 2005) and DFS (Pelosi et al, 2003b;Yoder et al, 2005). The close association we found between fascin immunoreactivity and tumour stage, tumour grade, the number and type of lymph node involvement, and distant metastasis indicates the major role of fascin in the progression of colonic adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the protein promotes cell locomotion (Yamashiro et al, 1998) and participates in the mechanical organisation of stress fibres (Adams, 1997). A definite overexpression of fascin has been reported in carcinomas of different organs, including oesophagus (Hashimoto et al, 2005a;Xie et al, 2005;Zhang et al, 2006), stomach (Hashimoto et al, 2004), colon (Jawhari et al, 2003;Hashimoto et al, 2006), pancreas (Maitra et al, 2002), breast (Grothey et al, 2000;Yoder et al, 2005), skin (Goncharuk et al, 2002), lung (Pelosi et al, 2003a, b;Choi et al, 2006), urinary bladder (Tong et al, 2005), and ovary (Hu et al, 2000) and the protein has been recently proposed as a novel biomarker for aggressive tumour behaviour (Hashimoto et al, 2005b(Hashimoto et al, , 2006Zhang et al, 2006). In colonic adenocarcinoma cell lines, fascin overexpression correlates with an increase in the formation of dynamic cell protrusions, proliferation, and invasiveness (Jawhari et al, 2003).…”

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Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

et al. 2007

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Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (Po0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas.

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Neurotrophin 3/TrkC‐regulated proteins in the human medulloblastoma cell line DAOY

et al. 2009

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Medulloblastoma (MB) is the most common malignant childhood brain tumor and high neurotrophin (NP) receptor TrkC mRNA expression was identified as a powerful independent predictor of favorable survival outcome. In order to determine downstream effector proteins of TrkC signaling, the MB cell line DAOY was stably transfected with a vector containing the full-length TrkC cDNA sequence or an empty vector control. A proteomic approach was used to search for expressional changes by two mass spectrometric methods and immunoblotting for validation of significant results. Multiple time points for up to 48 h following NP-3-induced TrkC receptor activation were chosen. Thirteen proteins from several pathways (nucleoside diphosphate kinase A, stathmin, valosin-containing protein, annexin A1, dihydropyrimidinase-related protein-3, DJ-1 protein, glutathione S-transferase P, lamin A/C, fascin, cofilin, vimentin, vinculin, and moesin) were differentially expressed and most have been shown to play a role in differentiation, migration, invasion, proliferation, apoptosis, drug resistance, or oncogenesis. Knowledge on effectors of TrkC signaling may represent a first useful step for the identification of marker candidates or reflecting probable pharmacological targets for specific treatment of MB.

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Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

Cited by 95 publications

References 32 publications

Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

Fascin overexpression in intraductal papillary mucinous neoplasms (adenomas, borderline neoplasms, and carcinomas) of the pancreas, correlated with increased histological grade

Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

Neurotrophin 3/TrkC‐regulated proteins in the human medulloblastoma cell line DAOY

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