Aberrant expression and phosphorylation of β-catenin in human colorectal cancer

Takayama, Takuya; Shiozaki, Hitoshi; Doki, Yuichiro; Oka, Hiroshi; Inoue, Masatoshi; Yamamoto, Makoto; Tamura, Shinji; Shibamoto, Sayumi; Ito, F.; Monden, Morito

doi:10.1038/bjc.1998.97

Cited by 76 publications

(60 citation statements)

References 36 publications

(33 reference statements)

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“…Similar alterations of ␤-catenin staining were seen in the UC-related and sporadic colorectal cancers. A decrease in membranous ␤-catenin expression and increases in cytoplasmic and nuclear ␤-catenin expression were observed in the UCrelated cancers, similar to that seen elsewhere in sporadic colorectal cancers (1,11). The increase in nuclear expression, however, was less frequent in the UC-related (48%) than in the sporadic tumors (81%).…”

Section: Discussionmentioning

confidence: 66%

“…Alterations of ␤-catenin expression are likely to affect both of these functions (18). ␤-catenin expression is frequently altered in sporadic colorectal cancers (1,2,7,11,19), whereas very little is known about its expression in UC-related cancers. In this study, immunohistochemistry was used to define the expression of ␤-catenin, and its two binding partners E-cadherin and APC, in UC-related colorectal cancers.…”

Section: Discussionmentioning

confidence: 99%

“…␤-catenin is a multifunctional protein that is involved in cell-cell interaction and transcriptional signaling (1)(2)(3)(4)(5). ␤-catenin expression is largely regulated by its two major binding partners, E-cadherin on the membrane and the adenomatous polyposis coli (APC) protein in the cytoplasm (6).…”

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confidence: 99%

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Altered Distribution of β-Catenin, and Its Binding Proteins E-Cadherin and APC, in Ulcerative Colitis–Related Colorectal Cancers

et al. 2001

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The ␤-catenin pathway plays a central role in transcriptional signaling and cell-cell interactions in colonic epithelium. Alterations of the expression of ␤-catenin, and its binding partners E-cadherin and the adenomatous polyposis coli protein (APC), are frequent events in sporadic colorectal cancer. Ulcerative colitis (UC)-related cancers originate in a field of chronic inflammation and therefore may have different alterations in the ␤-catenin pathway than sporadic cancers. To test this hypothesis, expression and subcellular localization of ␤-catenin, E-cadherin, and APC were detected by immunohistochemistry in paraffin sections from 33 UC-related and 42 sporadic colorectal cancers. Although ␤-catenin and E-cadherin expression were predominantly limited to the lateral cell membrane in normal colonic epithelium, both tumor groups showed an overall shift from membranous to cytoplasmic expression for these proteins. An increase in nuclear localization of ␤-catenin and a decrease in cytoplasmic APC expression also were seen in both cancer groups compared with normal epithelium. Abnormal ␤-catenin expression was more closely linked to E-cadherin alterations in UC-related cancers than in sporadic cancers. In contrast, abnormal ␤-catenin expression was more closely linked to APC alterations in sporadic cancers than in UCrelated cancers. These data suggest that alterations of the ␤-catenin pathway are important in both UC-related and sporadic colorectal cancers. However, differences in the expression patterns of ␤-catenin, E-cadherin, and APC between UCrelated and sporadic colorectal cancers suggest that the specific alterations in this pathway may differ in these two cancer groups.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Altered Distribution of β-Catenin, and Its Binding Proteins E-Cadherin and APC, in Ulcerative Colitis–Related Colorectal Cancers

et al. 2001

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“…More recent work has confirmed that tyrosine phosphorylation of β-catenin may participate in regulation of the cadherin-catenin complex in vivo (Takayama et al, 1998). Abnormal expression of each of the main components of the complex (E-cadherin, α-, β-catenin and plakoglobin) have been demonstrated in gastric cancer, and are commoner in the diffuse, poorly differentiated than in the intestinal, more well-differentiated histological type (Jawahari et al, 1997).…”

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confidence: 95%

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

1999

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Summary β-catenin, a component of the E-cadherin-catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of β-catenin is common in colorectal neoplasia. β-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular β-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, β-catenin and α-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, α-and β-catenins using microwave unmasking and an avidin-biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of β-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P = 0.0014), and was associated with poor differentiation (P = 0.0015) and short survival (P = 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of β-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P = 0.02). Neither E-cadherin or α-catenin expression correlated with survival. Reduced membranous expression of β-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in β-catenin expression from those found in colon cancer merit further study.

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“…Possible risk factors for lymph node metastasis in submucosal invasive colorectal carcinoma include the depth of submucosal invasion, poorly differentiated histology, lymphatic vessel invasion, expression of vascular endothelial growth factor-A and -C, and expression of β-catenin (Takayama et al 1998;Maeda et al 2003;Kojima et al 2005;Walgenbach-Bruenagel et al 2006;Liang et al 2006;Saad et al 2006;Kaneko et al 2007a;Ishii et al 2009). Several studies have reported that tumor budding is a histological risk factor for lymph node metastasis of colorectal carcinoma (Hori et al 2005;Park et al 2005;Masaki et al 2006;Kaneko et al 2007b).…”

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confidence: 99%

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

Umemura

Takagi

Shimada

et al. 2013

Tohoku J. Exp. Med.

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Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

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Aberrant expression and phosphorylation of β-catenin in human colorectal cancer

Cited by 76 publications

References 36 publications

Altered Distribution of β-Catenin, and Its Binding Proteins E-Cadherin and APC, in Ulcerative Colitis–Related Colorectal Cancers

Altered Distribution of β-Catenin, and Its Binding Proteins E-Cadherin and APC, in Ulcerative Colitis–Related Colorectal Cancers

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

Prognostic and Diagnostic Significance of Tumor Budding Associated with β-Catenin Expression in Submucosal Invasive Colorectal Carcinoma

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