NHE-RF, a Merlin-Interacting Protein, Is Primarily Expressed in Luminal Epithelia, Proliferative Endometrium, and Estrogen Receptor-Positive Breast Carcinomas

Stemmer‐Rachamimov, Anat; Wiederhold, Thorsten; Nielsen, G. Petur; James, Marianne F.; Pinney-Michalowski, Denise; Roy, Jennifer E.; Cohen, Wendy A.; Ramesh, Vijaya; Louis, David N.

doi:10.1016/s0002-9440(10)63944-2

Cited by 90 publications

(115 citation statements)

References 19 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…EBP50 is reported to increase in human breast cancer and may have an oncogenic function. 19 We found over-expression of EBP50 and a close association between EBP50 and ␤-catenin accumulation in human HCC. Our study also revealed that EBP50 potentiates ␤-catenin/TCF-mediated transcription.…”

mentioning

confidence: 63%

EBP50, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma

Shibata¹

2003

Hepatology

146

View full text Add to dashboard Cite

“…It was also previously reported that EBP50 is overexpressed and redistributed to the cytoplasm and/or nucleus of proliferative cells in hepatocellular carcinoma 8 and in estrogen stimulated-tissues, ie, in endometrium and breast tumors. 7,9,10 Although EBP50 was first postulated as a mitogenic factor, 6 it was subsequently shown to act either as an oncogene 8,9,11,13 or as a tumor suppressor, 14 -16,33,34 and so far its actual impact on cell proliferation has been unclear. Here, on the basis of gene silencing, we could clearly show that EBP50 controls proliferation positively in biliary epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The EBP50 gene possesses 13 half-estrogen responsive elements and is overexpressed in response to estrogens in proliferative mammary and endometrial cells. 4,7,9,10,43 Notably, 17␤-estradiol was recently shown to increase the amount of EBP50 in the nuclear fraction of human airway epithelial cells. 44 In addition, cholangiocyte proliferation is regulated by cyclic AMP, 45 which has also been shown to induce an intracellular redistribution of EBP50 in renal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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

show abstract

NHE-RF, a Merlin-Interacting Protein, Is Primarily Expressed in Luminal Epithelia, Proliferative Endometrium, and Estrogen Receptor-Positive Breast Carcinomas

Cited by 90 publications

References 19 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, a β-catenin-associating protein, enhances Wnt signaling and is over-expressed in hepatocellular carcinoma

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

Contact Info

Product

Resources

About