E-Cadherin Regulates the Association between β-Catenin and Actinin-4

Hayashida, Yasuharu; Honda, Kazufumi; Idogawa, Masashi; Ino, Yoshinori; Ono, M.; Tsuchida, Akihiko; Aoki, Tatsuya; Hirohashi, Setsuo; Yamada, Tesshi

doi:10.1158/0008-5472.can-05-0718

Cited by 109 publications

(116 citation statements)

References 47 publications

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“…Also, the association of actinin-4 and b-catenin was suppressed by transfection with E-cadherin cDNA, but induced by interfering RNA for E-cadherin. 38 These findings appear compatible with the present Actinin-4 and ovarian cancer S Yamamoto et al data, and suggest that molecular and functional association occurs between actinin-4 and b-catenin in ovarian carcinomas.…”

Section: Actinin-4 and Ovarian Cancer S Yamamoto Et Alsupporting

confidence: 89%

“…Of these, Hayashida et al 38 recently demonstrated that, in human colorectal cancer cells, actinin-4 recruits b-catenin into the actin-rich cytoplasmic portion when E-cadherin expression is decreased. Also, the association of actinin-4 and b-catenin was suppressed by transfection with E-cadherin cDNA, but induced by interfering RNA for E-cadherin.…”

Section: Actinin-4 and Ovarian Cancer S Yamamoto Et Almentioning

confidence: 99%

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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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Section: Actinin-4 and Ovarian Cancer S Yamamoto Et Alsupporting

confidence: 89%

Section: Actinin-4 and Ovarian Cancer S Yamamoto Et Almentioning

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

Self Cite

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“…These epithelial-stromal transition spots might be one of the possible molecular therapeutic targets. E-cadherin is found to be involved in the regulation of β-catenin and other molecules in cell adhesion processes [40]. By using microarrays and transcriptional intervention, Kuphal and Behrens, described how E-cadherin affects the Wnt pathway in CRC [41].…”

Section: Discussionmentioning

confidence: 99%

Expression of β-Catenin and E-Cadherin, their Clinical Significance and Association with Complexity Index of Colon Carcinoma

Ahmad¹,

Hahn-Strömberg²

2016

Adv Genet Eng

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Cell-cell adhesion and communication relies greatly on the E-cadherin/catenin system. Deregulation in this system may result in phenotypic change, which may create an opportunity for tumor cells to differentiate, metastasize and invade neighbouring tissue. In this study, we aimed to assess the protein expression of E-cadherin and β-catenin in the patients diagnosed with colon carcinoma correlating the levels with growth pattern of tumors using complexity index analysis as well as clinical and pathological features of the patients.129 colon carcinoma patients were selected to evaluate the protein expression of E-cadherin and β-catenin through immunohistochemical staining. Complexity index of randomly selected patients diagnosed with colon carcinoma was calculated to examine the growth pattern of the tumor.Expression of adhesion proteins was significantly perturbed in colon carcinoma patients as compared with normal mucosa (p<0.05). Similarly the growth pattern of tumor i.e., complexity index value was significantly related to differentiation of the tumor (p=0.002) and Duke's stages (p=0.026).Our results suggest that E-cadherin and β-catenin may play an indicative role in colorectal cancer invasion and disease progression which may act as prognostic markers in colorectal carcinoma. Also complexity index and adhesive proteins distribution are two independent markers which should aid the development of novel strategies for prevention as well as individual treatment of colon carcinoma.

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“…7 Recently, it was demonstrated that high cytoplasmic expression of actinin-4, a modulator of the cytoskeleton, is predominantly observed in budding cells of colorectal carcinoma. 29 Furthermore, high levels of actinin-4 are associated with increased cell motility. 30 Although it remains elusive if there is a causal relation between cytoplasmic Ep-CAM and actinin-4 expression, it is tempting to speculate that both proteins are closely involved in tumor budding.…”

Section: Discussionmentioning

confidence: 99%

Loss of membranous Ep-CAM in budding colorectal carcinoma cells

et al. 2007

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Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of b-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this study, we hypothesize that the epithelial cell adhesion molecule (Ep-CAM) is involved in tumor budding. In order to address this question, we performed immunohistochemistry on Ep-CAM using three different antibodies (monoclonal antibodies Ber-ep4 and 311-1K1 and a polyclonal antibody) and a double staining on b-catenin and Ep-CAM. In addition, Ep-CAM mRNA was monitored with mRNA in situ hybridization. Subsequently, we determined the effect of Ep-CAM staining patterns on tumor spread in rectal cancer. In contrast to the tumor mass, budding cells of colorectal carcinoma displayed lack of membranous but highly increased cytoplasmic Ep-CAM staining and nuclear translocation of b-catenin. mRNA in situ hybridization suggested no differences in Ep-CAM expression between the invasive front and the tumor mass. Importantly, reduced Ep-CAM staining at the invasive margin of rectal tumor specimens (n ¼ 133) correlated significantly with tumor budding, tumor grade and an increased risk of local recurrence (P ¼ 0.001, P ¼ 0.04 and P ¼ 0.03, respectively). These data demonstrate abnormal processing of Ep-CAM at the invasive margin of colorectal carcinomas. Our observations indicate that loss of membranous Ep-CAM is associated with nuclear b-catenin localization and suggest that this contributes to reduced cell-cell adhesions, increased migratory potential and tumor budding.

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E-Cadherin Regulates the Association between β-Catenin and Actinin-4

Cited by 109 publications

References 47 publications

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

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

Expression of β-Catenin and E-Cadherin, their Clinical Significance and Association with Complexity Index of Colon Carcinoma

Loss of membranous Ep-CAM in budding colorectal carcinoma cells

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