Alterations of E-cadherin and β-catenin in gastric cancer

Chen, Huiping; Kristjánsdóttir, Steinunn; Jonasson, Jón G.; Magnússon, Jónas; Egilsson, Valgarður; Ingvarsson, Sigurður

doi:10.1186/1471-2407-1-16

Cited by 55 publications

(53 citation statements)

References 25 publications

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“…We observed that a-and b-catenin appeared in a granular cytoplasmic pattern in tumors. Our data are in partial agreement with the aberrant expression and localization of b-catenin that has been reported in a variety of human cancers including colon, 36 liver, 37 stomach, 38 pancreas, 39 bone, 40 and thyroid. 41 Reports that have studied the expression of b-catenin in human lung cancer remain controversial.…”

Section: Discussionsupporting

confidence: 80%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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Loss of the epithelial phenotype and disruption of adhesion molecules is a hallmark in the epithelialmesenchymal transition (EMT) reported in several types of cancer. Most of the studies about the relevance of adhesion and junction molecules in lung cancer have been performed using established tumors or in vitro models. The sequential molecular events leading to EMT during lung cancer progression are still not well understood. We have used a rat model for multistep lung carcinogenesis to study the status of adherens and tight junction proteins and mesenchymal markers during EMT. After silica-induced chronic inflammation, rats sequentially develop epithelial hyperplasia, preneoplastic lesions, and tumors such as adenocarcinomas and squamous cell carcinomas. In comparison with normal and hyperplastic bronchiolar epithelium and with hyperplastic alveolar type II cells, the expression levels of E-cadherin, a-catenin and b-catenin were significantly reduced in adenomatoid preneoplastic lesions and in late tumors. The loss of E-cadherin in tumors was associated with its promoter hypermethylation. a-and b-catenin dysregulation lead to cytoplasmic accumulation in some carcinomas. No nuclear b-catenin localization was found at any stage of any preneoplastic or neoplastic lesion. Zonula occludens protein-1 was markedly decreased in 66% of adenocarcinomas and in 100% squamous cell carcinomas. The mesenchymal-associated proteins N-cadherin and vimentin were analyzed as markers for EMT. N-cadherin was de novo expressed in 32% of adenocarcinomas and 33% of squamous cell carcinomas. Vimentin-positive tumor cells were found in 35% of adenocarcinomas and 88% of squamous cell carcinomas. Mesenchymal markers were absent in precursor lesions, both hyperplastic and adenomatoid. The present results show that silica-induced rat lung carcinogenesis is a good model to study EMT in vivo, and also provide in vivo evidence suggesting that the changes in cell-cell adhesion molecules are an early event in lung carcinogenesis, while EMT occurs at a later stage.

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Section: Discussionsupporting

confidence: 80%

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Blanco

Vicent

Elizegi

et al. 2004

Laboratory Investigation

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“…As a key regulator of the differentiated epithelial phenotype, E-cadherin plays a critical role in the suppression of tumour invasion, and its function is required for the maintenance of stable adherens junctions and epithelial cell polarity (Takeichi, 1991;Perez-Moreno et al, 2003). Occurrence of altered E-cadherin expression has been correlated with dedifferentiation, increased risk of local invasion and metastatic disease, and recurrence and poor prognosis in a variety of carcinomas, for example, breast, uterine cervix, or gastric carcinomas (Moll et al, 1993;Fujimoto et al, 1997;Jawhari et al, 1997;Jeffers et al, 1997;Huiping et al, 2001). Previous studies have shown that reduced expression of E-cadherin in ovarian cancer is associated with the invasive phenotype, advancing tumour stage, lower 5-year survival rate, and poor recurrence-free survival (Faleiro-Rodrigues et al, 2004;Imai et al, 2004;Marques et al, 2004;Voutilainen et al, 2006) but not much is known about the underlying mechanisms of E-cadherin downregulation.…”

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confidence: 99%

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

et al. 2007

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Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (Po0.001). This correlation was found for Snail expression as well (Po0.001). There was a significant (P ¼ 0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P ¼ 0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P ¼ 0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

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“…[15][16][17][18][19] Indeed, downregulation or abnormal expression of E-cadherincatenin proteins has been reported to be associated with poor histologic differentiation of tumors, increased risk of peritoneal metastasis, and poor patient outcome in ovarian cancer as well as in various solid cancers at other primary sites. [19][20][21][22][23][24] Although, for disease progression, ovarian cancer cells should require cell motility besides loss of cellto-cell adhesion, the molecular backgrounds underlying this process is still unclear.…”

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confidence: 99%

Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

Yamamoto

Tsuda

Honda³

et al. 2007

Modern Pathology

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Actinin-4 is an isoform of non-muscular a-actinin and actin-bundling protein. By enhancing cell motility, actinin-4 shows different biological properties from another isoform of non-muscular actinin 'actinin-1' and variable clinicopathological implications of actinin-4 have been demonstrated in some human malignancies such as breast cancers, lung cancers, and colorectal cancers. We herein described the clinicopathological and prognostic significance of actinin-4 expression in ovarian cancers. Actinin-4 expression was analyzed immunohistochemically in 265 primary ovarian carcinomas: 116 serous, 71 clear cell, 43 endometrioid, and 35 mucinous adenocarcinomas. With reference to endothelial immunoreactivity, cytoplasmic expression of actinin-4 was classified as either low (including negative) or high. Then, various parameters such as patients' characteristics, histopathological findings including E-cadherin and b-catenin immunoreactivity, and clinical outcome, were compared between groups showing differences in the intensity or intracellular distribution of actinin-4 immunoreactivity. High expression of actinin-4 was demonstrated in 137 (57%) cases and was associated with serous histology (P ¼ 0.0075), high histological grade (Po0.0001), an advanced disease stage (P ¼ 0.036), a high degree of residual disease after initial surgery (P ¼ 0.0047), poor patient outcome (5-year survival: 52.4% in the high-expression group vs 71.9% in the low expression group, P ¼ 0.0043 by log-rank test), and also with reduced E-cadherin and preserved b-catenin expressions (P ¼ 0.0097 and 0.017, respectively). Nuclear immunoreactivity for actinin-4 was detected in 20 (7.5%) cases and was associated with low histological grade (P ¼ 0.0079) but not with other variables. Multivariate analysis showed that high actinin-4 expression was an independent prognostic factor for overall survival, as well as a high degree of residual disease and clear-cell histology. Accumulation of actinin-4 in the cytoplasm may be related to a higher propensity for tumor invasiveness and metastasis, probably by enhancing cell motility, and could be a novel prognostic indicator for patients with ovarian carcinomas.

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Alterations of E-cadherin and β-catenin in gastric cancer

Cited by 55 publications

References 25 publications

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

Altered expression of adhesion molecules and epithelial–mesenchymal transition in silica-induced rat lung carcinogenesis

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

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