Expression and clinicopathological significance of oestrogen‐responsive ezrin–radixin–moesin‐binding phosphoprotein 50 in breast cancer

Song, Jianning; Bai, Jining; Yang, Wenqiang; Gabrielson, Edward; Chan, DW; Zhang, Z

doi:10.1111/j.1365-2559.2007.02730.x

Cited by 58 publications

(90 citation statements)

References 35 publications

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“…EBP50 is present at the plasma membrane in physiological conditions, but often displays ectopic cytoplasmic expression in cholangiocarcinoma tumors. Similar cytoplasmic expression of EBP50 has been described in other human carcinomas, including breast, liver (hepatocellular carcinoma), brain and colon (Stemmer-Rachamimov et al, 2001;Shibata et al, 2003;Cardone et al, 2007;Song et al, 2007;Hayashi et al, 2010;Molina et al, 2010). In these tumors, we show an association between EBP50 cytoplasmic expression and the presence of EGFR at …”

Section: Loss Of Ebp50-egfr Interplay In Biliary Carcinomasupporting

confidence: 87%

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

et al. 2011

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Scaffold proteins form multiprotein complexes that are central to the regulation of intracellular signaling. The scaffold protein ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is highly expressed at the plasma membrane of normal biliary epithelial cells and binds epidermal growth factor receptor (EGFR), a tyrosine kinase receptor with oncogenic properties. This study investigated EBP50-EGFR interplay in biliary cancer. We report that in a collection of 106 cholangiocarcinomas, EBP50 was delocalized to the cytoplasm of tumor cells in 66% of the cases. Ectopic expression of EBP50 was correlated with the presence of satellite nodules and with the expression of EGFR, which was at the plasma membrane, implying a loss of interaction with EBP50 in these cases. In vitro, loss of interaction between EBP50 and EGFR was mimicked by EBP50 depletion using a small interfering RNA approach in human biliary carcinoma cells co-expressing the two proteins at their plasma membrane, and in which interaction between EBP50 and EGFR was validated. EBP50 depletion caused an increase in EGFR expression at their surface, and a sustained activation of the receptor and of its downstream effectors (extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3) in both basal and EGF-stimulated conditions. Cells lacking EBP50 showed epithelial-to-mesenchymal transition-associated features, including reduction in E-cadherin and cytokeratin-19 expression, induction of S100A4 and of the E-cadherin transcriptional repressor, Slug, and loss of cell polarity. Accordingly, depletion of EBP50 induced the disruption of adherens junctional complexes, the development of lamellipodia structures and the subsequent acquisition of motility properties. All these phenotypic changes were prevented upon inhibition of EGFR tyrosine kinase by gefitinib. These findings indicate that loss of EBP50 at the plasma membrane in tumor cells may contribute to biliary carcinogenesis through EGFR activation.

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Section: Loss Of Ebp50-egfr Interplay In Biliary Carcinomasupporting

confidence: 87%

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

et al. 2011

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“…Overexpression of NHERF1/EBP50 has been reported in breast cancer (5,6) and in 55% of hepatocellular carcinoma samples (7). Initially, overexpression of NHERF1/EBP50 has been correlated with lower tumor invasiveness in breast cancer cell lines (8).…”

Section: Introductionmentioning

confidence: 99%

“…These two independent studies however reached the same conclusions. They found that EBP50 overexpression is significantly associated with tumor stage, metastatic progression, poor prognosis and ER status (5,9). The expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells (10).…”

Section: Introductionmentioning

confidence: 99%

“…Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) is a post synaptic density-95/Disk-large/ZO-1 homologous domain-containing protein that is involved in the linkage of integral membrane proteins to the cytoskeleton and plays an important role in cell signaling (5). Overexpression of NHERF1/EBP50 has been reported in breast cancer (5,6) and in 55% of hepatocellular carcinoma samples (7).…”

Section: Introductionmentioning

confidence: 99%

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EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in gastric cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways

Dong

et al. 2012

Mol Med Report

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Abstract. 5-Fluorouracil (5-FU) plays an important role in the chemotherapy of advanced gastric cancer. However, genetic factors that affect therapeutic efficacy of 5-FU warrant further investigation. In the present study, using stable transfection of the ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) gene, we explored the genetic influences on 5-FU-induced apoptosis of human gastric cancer cells. Stable overexpression of the EBP50 gene was determined by reverse transcription polymerase chain reaction (RT-PCR) assay and western blot analysis. After treatment with 5-FU, cell growth activities in vitro were investigated by MTT assay. Cell apoptosis was evaluated by Hoechst 33258 staining and flow cytometry of Annexin V-FITC/PI staining. Compared with the BGC823 or BGC823/neo cells, EBP50 mRNA and protein levels in the BGC823/EBP50 cells (EBP50-transfected BGC823 cells) were markedly higher. Chemosensitivity and apoptosis rates of the BGC823/EBP50 cells were higher compared to the BGC823 and BGC823/neo cells following treatment with 5-FU. Stable overexpression of extrinsic EBP50 distinctly increases the 5-FU-induced apoptosis of gastric cancer cells, and is a novel strategy by which to improve the chemosensitivity of gastric cancer to 5-FU.

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“…6 In tumors, ie, in hepatocellular or breast carcinomas, and in non tumor proliferative tissue such as the endometrium, EBP50 can be overexpressed and redistributed to the cytoplasm and/or nucleus of epithelial cells. [7][8][9][10] In addition, some EBP50 binding partners, eg, platelet-derived growth factor or epidermal growth factor receptors, PTEN, ␤-catenin, and Pin1 signaling molecules, are directly involved in cell proliferation. 8,[11][12][13][14][15] However, the exact impact of EBP50 on cell proliferation remains unclear.…”

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confidence: 99%

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

Fouassier

Rosenberg

Mergey

et al. 2009

The American Journal of Pathology

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Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) anchors and regulates apical membrane proteins in epithelia. EBP50 is inducible by estrogen and may affect cell proliferation, although this latter function remains unclear. The goal of this study was to determine whether EBP50 was implicated in the ductular reaction that occurs in liver disease. EBP50 expression was examined in normal human liver, in human cholangiopathies (ie, cystic fibrosis, primary biliary cirrhosis, and primary sclerosing cholangitis), and in rats subjected to bile-duct ligation. The regulation of EBP50 by estrogens and its impact on proliferation were assessed in both bile duct-ligated rats and Mz-Cha-1 human biliary epithelial cells. Analyses of cell isolates and immunohistochemical studies showed that in normal human liver, EBP50 is expressed in the canalicular membranes of hepatocytes and, together with ezrin and cystic fibrosis transmembrane conductance regulator, in the apical domains of cholangiocytes. In both human cholangiopathies and bile duct-ligated rats, EBP50 was redistributed to the cytoplasmic and nuclear compartments. EBP50 underwent a transient increase in rat cholangiocytes after bile-duct ligation, whereas such expression was down-regulated in ovariectomized rats. In addition, in Mz-Cha-1 cells, EBP50 underwent upregulation and intracellular redistribution in response to 17␤-estradiol, whereas its proliferation was inhibited by siRNA-mediated EBP50 knockdown. These results indicate that both the expression and distribution of EBP50 are regulated by estrogens and contribute to the proliferative response in biliary epithelial cells. (Am J

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Expression and clinicopathological significance of oestrogen‐responsive ezrin–radixin–moesin‐binding phosphoprotein 50 in breast cancer

Abstract: Oestrogen-responsive EBP50 may play an important role in tumour progression and might be a potential marker of invasiveness for breast cancer.

Cited by 58 publications

References 35 publications

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

Loss of EBP50 stimulates EGFR activity to induce EMT phenotypic features in biliary cancer cells

EBP50 gene transfection promotes 5-fluorouracil-induced apoptosis in gastric cancer cells through Bax- and Bcl-2-triggered mitochondrial pathways

Ezrin-Radixin-Moesin-Binding Phosphoprotein (EBP50), an Estrogen-Inducible Scaffold Protein, Contributes to Biliary Epithelial Cell Proliferation

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