E-cadherin but not N-cadherin expression is correlated with the intracellular distribution of catenins in human hepatocellular carcinomas.

Nuruki, Kensuke; Toyoyama, Hironobu; Ueno, S.; Hamanoue, Masahiro; Tanabe, Gen; Aikou, Takashi; Ozawa, Masayuki

doi:10.3892/or.5.5.1109

Cited by 21 publications

(19 citation statements)

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“…In accordance with previous reports [22,23] , the expressions of all the members of E-cadherin/catenin complex were down-regulated in HCC, among of which the reduced expression of α-catenin was found most frequently. The expression of these five molecules was inversely correlated with tumor differentiation degree, thus all of them may be considered as good differentiation markers of HCC.…”

Section: Discussionsupporting

confidence: 92%

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Zhai¹,

Yan²,

Li³

et al. 2008

WJG

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AIM:To examine the immunoreactivity of E-cadherin a n d fo u r s u b type s of c at e nin fami ly in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/ catenin complex and clinicopathologic parameters of HCC patients. METHODS: An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. RESULTS: Reduced expression of E-cadherin, α-, β-, γ-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively).A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively).In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P = 0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with α-, β-, γ-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. CONCLUSION: Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.

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Section: Discussionsupporting

confidence: 92%

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Zhai¹,

Yan²,

Li³

et al. 2008

WJG

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“…An increase in ␤-catenin gene expression results in a concomitant increase in E-cadherin expression, effectively reducing the activity of ␤-catenin . The loss of E-cadherin is a hallmark of many cancers, resulting in increased cytoplasmic stabilization of ␤-catenin (Behrens et al, 1993;Nuruki et al, 1998;Calvisi et al, 2004b;Jeanes et al, 2008). We observed a marked decrease in E-cadherin expression in the livers of FXR-KO mice, which is consistent with increased ␤-catenin activation.…”

Section: Discussionsupporting

confidence: 72%

Increased Activation of the Wnt/β-Catenin Pathway in Spontaneous Hepatocellular Carcinoma Observed in Farnesoid X Receptor Knockout Mice

Wolfe

Thomas²,

Edwards³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

126

117

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Farnesoid X receptor (FXR), the primary bile acid-sensing nuclear receptor, also is known for its anticancer properties. It is known that FXR deficiency in mice results in spontaneous hepatocellular carcinoma (HCC), but the mechanisms are not completely understood. We report that sustained activation of the Wnt/␤-catenin pathway is associated with spontaneous HCC in FXR-knockout (KO) mice. HCC development was studied in FXR-KO mice at 3, 8, and 14 months of age. No tumors were observed at either 3 or 8 months, but the presence of HCC was observed in 100% of the FXR-KO mice at the age of 14 months. Further analysis revealed no change in ␤-catenin activation in the livers of 3-month-old FXR-KO mice, but a moderate increase was observed in 8-month-old FXR-KO mice. ␤-Catenin activation further increased significantly in 14-month-old tumor-bearing mice. Further analysis revealed that two independent mechanisms might be involved in ␤-catenin activation in the livers of FXR-KO mice. Activation of canonical Wnt signaling was evident as indicated by increased Wnt4 and dishevelled expression along with glycogen synthase kinase-3␤ inactivation. We also observed decreased expression of E-cadherin, a known regulator of ␤-catenin, in FXR-KO mice. The decrease in E-cadherin expression was accompanied by increased expression of its transcriptional repressor, Snail. Consistent with the increased HCC in FXR-KO mice, we observed a significant decrease in FXR expression and activity in human HCC samples. Taken together, these data indicate that a temporal increase in the activation of Wnt/␤-catenin is observed during spontaneous HCC development in FXR-KO mice and is potentially critical for tumor development.

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“…These data are in general agreement with previous studies in which E-cadherin was found to be down-regulated in 33% to 53% of HCC cases, and frequent up-regulation was also noted in 2 reports. 12,13,15,38 In tumor model systems, down-regulation of E-cadherin has been associated with loss of intercellular adhesiveness, tumor dedifferentiation, and invasive potential. 39 We therefore searched for associations between E-cadherin expression levels and histopathologic parameters.…”

Section: Resultsmentioning

confidence: 99%

Altered expression of E-cadherin in hepatocellular carcinoma: Correlations with genetic alterations, β-catenin expression, and clinical features

et al. 2002

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H epatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of death by cancer worldwide. Epidemiologic studies have shown that more than 70% of HCC cases are linked to chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Other risk factors include alcohol-related cirrhosis, dietary intake of aflatoxin B1 in some tropical areas, and inherited metabolic disorders such as tyrosinemia, hemochromatosis, and ␣1-antitrypsin deficiency. Recent insights into the mechanisms underlying HCC development have been provided by genome-wide allelotype studies and comparative genomic hybridization, showing numerous chromosomal changes during tumor development and progression. 1-5 These studies have led to the identification of a number of host factors as culprits in liver malignancy. Notably, allelic imbalance at chromosome 17p13 and frequent mutations of the p53 gene have been correlated with exposure to aflatoxin B1 and chronic HBV infection. 3 Mutations of ␤-catenin or its binding partner axin1, leading to abnormal activation of the Wnt pathway, have been implicated in about one third of HCC cases. 6,7 Among other common alterations, the long arm of chromosome 16 is a region of frequent loss of heterozygosity (LOH) in HCC, with deletion rates ranging from 28% to 70% in different studies. [8][9][10][11] This chromosomal arm carries a cluster of cadherin genes located at 16q22.1, and it has been proposed that deregulation of E-cadherin might be involved in liver carcinogenesis. [12][13][14][15]

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E-cadherin but not N-cadherin expression is correlated with the intracellular distribution of catenins in human hepatocellular carcinomas.

Cited by 21 publications

References 0 publications

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

Increased Activation of the Wnt/β-Catenin Pathway in Spontaneous Hepatocellular Carcinoma Observed in Farnesoid X Receptor Knockout Mice

Altered expression of E-cadherin in hepatocellular carcinoma: Correlations with genetic alterations, β-catenin expression, and clinical features

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