Prognostic significance of snail expression in hilar cholangiocarcinoma

Kong, Dalu; Liang, Jun; Li, Rong; Liu, Shihai; Wang, Jigang; Zhang, Kejun; Chen, Dong

doi:10.1590/s0100-879x2012007500070

Cited by 9 publications

(9 citation statements)

References 29 publications

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“…Tumor cells from human iCCA expressing both the mesenchymal marker SNAIL in the nucleus and the biliary epithelial marker CK19 were identified by double immunofluorescence staining, providing conclusive evidence for the presence of EMT traits in malignant cholangiocytes [55]. While not detected in normal biliary epithelium, SNAIL mRNA and protein levels are markedly expressed in CCA, with a sub-cellular localization of the protein in the nuclei of iCCA and eCCA tumor cells [24,32,37,39,48,56]. High expression of SNAIL transcripts was correlated with the presence of metastasis [56].…”

Section: Emt-inducing Transcription Factors (Emt-tfs)mentioning

confidence: 87%

“…A reduction of E-cadherin immunostaining was observed in 16.5-82.1% of iCCA [21, 24-26, 29, 31, 32, 34-36] and eCCA [18,37,39,40]. Although, down-regulation of E-cadherin in iCCA has been correlated with poor tumor differentiation, tumor size, advanced pTNM stage, intrahepatic metastasis and lymph node metastasis [25,26,29,31,32,36], its prognostic value is still controversial.…”

Section: Disruption Of Intercellular Junctionsmentioning

confidence: 99%

“…High expression of SNAIL transcripts was correlated with the presence of metastasis [56]. Nuclear overexpression of SNAIL protein was associated with aggressive parameters and poor prognosis in both iCCA (28.6-48.6% of cases) and eCCA (38-54% of cases), and predicted worse OS and DFS [24,32,39,48]. Consistently with its repressing function on E-cadherin, increased SNAIL mRNA levels were negatively associated with E-cadherin transcripts and protein expression [32,56].…”

Section: Emt-inducing Transcription Factors (Emt-tfs)mentioning

confidence: 99%

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Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

126

122

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Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a center of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analyzed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT. 4Key Point Box -EMT is an early event of metastasis that endows tumor cells with invasive properties enabling them to spread toward other territories.-EMT contributes to CCA progression and chemoresistance.-The three families of transcription factors that regulate epithelial and mesenchymal marker expression during EMT (SNAIL, TWIST and ZEB) contribute to CCA progression.-Cells of CCA microenvironment, and not only cancer cells, lead to the activation of EMT.

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Section: Emt-inducing Transcription Factors (Emt-tfs)mentioning

confidence: 87%

Section: Disruption Of Intercellular Junctionsmentioning

confidence: 99%

Section: Emt-inducing Transcription Factors (Emt-tfs)mentioning

confidence: 99%

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Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

126

122

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“…Reduced or aberrant expression of beta‐catenin and P‐120 catenin was also reported in 39–97% and 74% of CCA without Ov infection, respectively . In this connection, epithelial‐mesenchymal transition (EMT) was observed in a subset of CCA, where master regulators of the transcription, Snail and Slug, showed higher expression in 18/47 (38%) and 21/36 (42%), respectively, of CCAs with more invasive phenotypes . It is particularly interesting that cytokines released from activated human macrophages were shown to induce EMT markers in cholangiocarcinoma cells .…”

Section: Aberrant Cell Adhesion In Cca Associated With Ov Infectionmentioning

confidence: 96%

Genomic and transcriptional alterations of cholangiocarcinoma

Ito

Sakurai-Yageta

Goto

et al. 2014

J Hepato Biliary Pancreat

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Cholangiocarcinoma (CCA) is one of the representative cancers refractory to any therapeutic approach. The incidence of CCA is highest in the northeastern part of Thailand, where chronic inflammation caused by liver fluke (Opisthorchis viverrini: Ov) infection is a major etiologic factor. The incidence of CCA is also increasing in other countries, including Japan. Here, we overview the genetic and transcriptional alterations of CCA with and without association with Ov infection. CCA with Ov shows enhanced expression of the genes involved in xenobiotic metabolism and chronic inflammatory responses, including cytokine signaling, whereas CCA without Ov shows enhanced expression of growth factor signaling, such as HER2. Exome and the following prevalence sequencing identified mutations of the BAP1, ARID1A, IDH1 and IDH2 genes in CCA, in addition to the high incidence of known mutations in the TP53, KRAS2 SMAD4, and CDKN2A genes, suggesting the role of chromatin modulators in CCA pathogenesis. CCA with Ov shows significantly higher incidence of the TP53 gene mutation, whereas CCA without Ov showed significantly more frequent mutations of the BAP1, IDH1 and IDH2 genes. However, CCAs with Ov and without Ov share a similar mutation spectrum dominated by C : G > T : A transitions mainly at CpG dinucleotides, suggesting that CCA shares etiologic factors with pancreatic ductal carcinoma but not with hepatocellular carcinoma. Comprehensive analyses of the genetic and transcriptional alterations of CCA with and without Ov infection would provide useful information for the prevention, early diagnosis, and treatment of CCA.

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“…Snail and Slug are associated with metastasis and poor outcome in several cancers, such as hilar cholangiocarcinoma, esophageal squamous cell carcinoma and oral squamous cell carcinoma [11][12][13]. e increase expression of Snail and Slug is also correlated with higher histological grades and reduced relapsefree survival in patients with breast carcinoma [14].…”

mentioning

confidence: 99%

Snail family proteins in cervical squamous carcinoma: Expression and significance

Zhang¹,

Ying²,

Xu³

et al. 2013

CIM

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Purpose: Epithelial-mesenchymal transition (EMT) is crucial for tumor progression and metastasis. Snail family members, including Snail, Slug and Smuc, are the transcription factors that repress E-cadherin expression and induce epithelial-mesenchymal transition in some tumor tissues. In this study, the expression of snail family proteins in cervical squamous cancers was evaluated. Methods: A series of 144 samples, comprising 28 cases of normal cervical tissues and 116 cases of squamous cell carcinoma (SCC), were used for analysis. The expression of Snail, Slug, Smuc, E-cadherin and vimentin was assessed in the tissues by immunohistochemistry and was statistically analyzed by SPSS13.0. Results: The increase in nuclear expression of snail and smuc was associated with down-regulation of E-cadherin and up-regulation of vimentin. The nuclear expression of Snail and Smuc was positively associated with lymph node metastasis of the SCC, and the nuclear expression of Snail was also positively related with histological differentiation. In contrast, tumor size, histological differentiation, lymph node metastasis and stages of the SCC were not associated with the expression of Slug, cytpolasmic Smuc or cytoplasm levels of Snail. Conclusion: Snail and Smuc proteins, but not Slug, may contribute to the onset of EMT in SCC. Inhibiting the expression of Snail and Smuc might be a potential therapeutic target for the treatment of metastasis and invasion of cervical carcinomas.

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Prognostic significance of snail expression in hilar cholangiocarcinoma

Cited by 9 publications

References 29 publications

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Genomic and transcriptional alterations of cholangiocarcinoma

Snail family proteins in cervical squamous carcinoma: Expression and significance

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