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

Puppa, Giacomo; Maisonneuve, Patrick; Sonzogni, Angelica; Masullo, Michele; Chiappa, Antonio; Valerio, Maria Rosaria; Zampino, Maria Giulia; Franceschetti, Ilaria; Capelli, Paola; Chilosi, Marco; Menestrina, Fabio; Viale, Giuseppe; Pelosi, Giuseppe

doi:10.1038/sj.bjc.6603690

Cited by 47 publications

(71 citation statements)

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“…The expression of fascin has been shown to be low or absent in the normal epithelium of a number of tissues, but deregulated in cancer (Hashimoto et al, 2005). We, and others, have recently shown that fascin expression is readily detected in the epithelial component of colorectal carcinomas (Jawhari et al, 2003;Hashimoto et al, 2006;Puppa et al, 2007). These data show that the expression of fascin represents a phenotypic change in colorectal carcinomas and that fascin is associated with a poorer prognosis in colorectal cancer patients (Hashimoto et al, 2006;Puppa et al, 2007).…”

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confidence: 70%

“…We, and others, have recently shown that fascin expression is readily detected in the epithelial component of colorectal carcinomas (Jawhari et al, 2003;Hashimoto et al, 2006;Puppa et al, 2007). These data show that the expression of fascin represents a phenotypic change in colorectal carcinomas and that fascin is associated with a poorer prognosis in colorectal cancer patients (Hashimoto et al, 2006;Puppa et al, 2007). To understand fully the role of fascin in colorectal tumorigenesis, it is important to determine at what stage it becomes deregulated.…”

Section: Discussionmentioning

confidence: 99%

“…Two recent studies have demonstrated that fascin expression correlates with a poor prognosis in colorectal cancers (Hashimoto et al, 2006;Puppa et al, 2007). Hashimoto et al (2006) found no correlation between the genetic origin of colorectal adenomas (FAP or sporadic) and fascin expression (Hashimoto et al, 2006).…”

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The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

et al. 2009

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BACKGROUND: Fascin is overexpressed in many cancers, including colorectal, but its role in the malignant transformation of benign colorectal adenomas is unclear. METHODS: Immunohistochemical analysis of fascin expression was carried out in resected human colorectal adenoma specimens. The effects of forced overexpression of fascin on adenoma cell motility were also analysed. RESULTS: We show fascin overexpression in adenomas increasing with tumour size, histological type, and degree of dysplasia and increased cell motility in adenoma cell lines following fascin transfection. CONCLUSION: These data suggest an important role for fascin in the malignant progression of colorectal tumours. Colorectal cancer development is widely accepted to involve the multifaceted progression of a benign lesion (adenoma) to invasive adenocarcinoma (hereafter referred to as 'carcinoma') by acquisition of a migratory, and ultimately invasive phenotype (Muto et al, 1975). The precise nature of the changes required for the malignant progression of adenomas remain poorly understood but prognosis is widely accepted to correlate with both the physical size and histological type of the adenomatous polyp, as well as the degree of cellular dysplasia displayed by the tumour cells (Muto et al, 1975).The changes in motile behaviour demonstrated by tumour cells require dynamic rearrangements in the actin cytoskeleton, which are governed by multiple actin-binding proteins (Matsudaira, 1994). The 55 kDa fascin-1 protein (hereafter be referred to simply as fascin) localises to the core actin bundles of spikes and filopodia at the leading edge of migratory cells, and has been shown to increase migration in several cell types (Adams, 2001;Kureishy et al, 2002). There now exists a plethora of reports showing a general trend across epithelial tissues with fascin being absent from normal epithelium and present in tumours of the same tissue origin (Hashimoto et al, 2005).We have previously shown that fascin is absent from normal colorectal epithelium but overexpressed in colorectal carcinomas (Sawhari et al, 2003). Two recent studies have demonstrated that fascin expression correlates with a poor prognosis in colorectal cancers (Hashimoto et al, 2006;Puppa et al, 2007). Hashimoto et al. (2006) found no correlation between the genetic origin of colorectal adenomas (FAP or sporadic) and fascin expression (Hashimoto et al, 2006). However, to date, no study has been reported analysing the expression and distribution of fascin in benign colorectal adenomas in relation to the clinical risk factors associated with malignant tumour progression.To understand the role of a gene during tumourigenesis, it is important to know at what stage it becomes deregulated. In the study presented here, we sought to determine this potential relationship between fascin expression and malignant progression in colorectal adenomas. We performed immunohistochemistry for fascin on colorectal adenoma specimens graded for the risk factors associated with malignant potential, namely pol...

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Section: Discussionmentioning

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The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

et al. 2009

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“…Consistently, irrespective of the tissue source of the tumor, primary carcinomas with high levels of fascin correlate with a clinically aggressive phenotype and poor prognosis (Maitra et al, 2002;Pelosi et al, 2003;Hashimoto et al, 2004Hashimoto et al, , 2005aHashimoto et al, ,b, 2006Yoder et al, 2005;Zigeuner et al, 2006). Whether fascin contributes functionally to metastasis is largely unknown; however, high fascin protein in the primary carcinoma has been correlated with local lymph node or distant metastases (Hashimoto et al, 2004;Puppa et al, 2007) or with an increased frequency of metastastic disease (Zigeuner et al, 2006). The fascin transcript is a component of a gene signature that correlates with breast cancer metastasis to the lung (Minn et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to Metastasis

Hashimoto

Parsons

Adams³

2007

MBoC

127

169

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Recurrence of carcinomas due to cells that migrate away from the primary tumor is a major problem in cancer treatment. Immunohistochemical analyses of human carcinomas have consistently correlated up-regulation of the actin-bundling protein fascin with a clinically aggressive phenotype and poor prognosis. To understand the functional and mechanistic contributions of fascin, we undertook inducible short hairpin RNA (shRNA) knockdown of fascin in human colon carcinoma cells derived from an aggressive primary tumor. Fascin-depletion led to decreased numbers of filopodia and altered morphology of cell protrusions, decreased Rac-dependent migration on laminin, decreased turnover of focal adhesions, and, in vivo, decreased xenograft tumor development and metastasis. cDNA rescue of fascin shRNAknockdown cells with wild-type green fluorescent protein-fascin or fascins mutated at the protein kinase C (PKC) phosphorylation site revealed that both the actin-bundling and active PKC-binding activities of fascin are required for the organization of filopodial protrusions, Rac-dependent migration, and tumor metastasis. Thus, fascin contributes to carcinoma migration and metastasis through dual pathways that impact on multiple subcellular structures needed for cell migration.

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“…Fascin is a 55 kDa cross-linking protein that localizes the core actin bundles of spikes and filopodia at the leading edge of migratory cells (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Fascin promotes the formation of tightly packed parallel bundles with F-actin (16,19,21).…”

Section: Introductionmentioning

confidence: 99%

Fascin expression and its potential significance in gastrointestinal stromal tumors

Özcan¹,

Karslioğlu²,

Günal³

et al. 2011

Turk J Gastroenterol

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

Cited by 47 publications

References 47 publications

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro

Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to Metastasis

Fascin expression and its potential significance in gastrointestinal stromal tumors

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