Staff View: Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.

Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.

Dysregulation of E-cadherin and β-catenin function in cell-cell adhesion is common in nasopharyngeal carcinoma (NPC) and correlates with metastatic disease. In this study, we examined the role of EGF-activated phosphatidylinositol 3-kinase (PI3K)-Akt signaling in E-cadherin and β-catenin regulation....

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Main Authors:	Wai, Kien Yip, Seow, Heng Fong
Format:	Article
Language:	English English
Published:	Elsevier 2012
Online Access:	http://psasir.upm.edu.my/id/eprint/24623/1/Activation%20of%20phosphatidylinositol%203.pdf http://psasir.upm.edu.my/id/eprint/24623/ http://www.elsevier.com/
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spelling	my.upm.eprints.246232015-10-09T07:19:00Z http://psasir.upm.edu.my/id/eprint/24623/ Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells. Wai, Kien Yip Seow, Heng Fong Dysregulation of E-cadherin and β-catenin function in cell-cell adhesion is common in nasopharyngeal carcinoma (NPC) and correlates with metastatic disease. In this study, we examined the role of EGF-activated phosphatidylinositol 3-kinase (PI3K)-Akt signaling in E-cadherin and β-catenin regulation. We found that reduced membranous E-cadherin and β-catenin expression was positively correlated with Akt phosphorylation in NPC tissues. EGF treatment disrupted cell-cell adhesion and resulted in mesenchymal morphological features in NPC cell lines (TW01, TW04, and TW06). Western blot analysis showed that the E-cadherin protein level was partially reduced in TW04 cells only and the β-catenin levels were not considerably affected upon EGF treatment. In contrast, quantitative real-time RT-PCR showed that the E-cadherin, but not β-catenin, mRNA levels were markedly reduced by EGF in all cell lines. Immunofluorescent staining revealed that E-cadherin and β-catenin appeared to be markedly reduced on the cell surface and more localized in the cytoplasm. Inhibition of PI3K by LY294002 did not abolish the EGF-induced downregulation of E-cadherin protein or mRNA in TW04 cells but moderately increased the β-catenin protein level in TW01 cells and mRNA level in TW06 cells. However, LY294002 substantially restored or increased cell surface E-cadherin and β-catenin in all EGF-treated cell lines, in concordance with the inhibition of cell morphological changes. Moreover, LY294002 significantly blocked EGF-driven cell invasion, correlating with the elevation of membranous E-cadherin and β-catenin levels. In conclusion, EGF-induced epithelial-to-mesenchymal transition may not be only dependent on downregulation of E-cadherin protein/mRNA but also on mislocalization of E-cadherin and β-catenin. The mechanisms involved may be related, at least in part, to the PI3K-Akt pathway. Elsevier 2012-05 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/24623/1/Activation%20of%20phosphatidylinositol%203.pdf Wai, Kien Yip and Seow, Heng Fong (2012) Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells. Cancer Letters, 318 (2). pp. 162-172. ISSN 0304-3835; ESSN:1872-7980 http://www.elsevier.com/ 10.1016/j.canlet.2011.12.018 English
institution	Universiti Putra Malaysia
building	UPM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Putra Malaysia
content_source	UPM Institutional Repository
url_provider	http://psasir.upm.edu.my/
language	English English
description	Dysregulation of E-cadherin and β-catenin function in cell-cell adhesion is common in nasopharyngeal carcinoma (NPC) and correlates with metastatic disease. In this study, we examined the role of EGF-activated phosphatidylinositol 3-kinase (PI3K)-Akt signaling in E-cadherin and β-catenin regulation. We found that reduced membranous E-cadherin and β-catenin expression was positively correlated with Akt phosphorylation in NPC tissues. EGF treatment disrupted cell-cell adhesion and resulted in mesenchymal morphological features in NPC cell lines (TW01, TW04, and TW06). Western blot analysis showed that the E-cadherin protein level was partially reduced in TW04 cells only and the β-catenin levels were not considerably affected upon EGF treatment. In contrast, quantitative real-time RT-PCR showed that the E-cadherin, but not β-catenin, mRNA levels were markedly reduced by EGF in all cell lines. Immunofluorescent staining revealed that E-cadherin and β-catenin appeared to be markedly reduced on the cell surface and more localized in the cytoplasm. Inhibition of PI3K by LY294002 did not abolish the EGF-induced downregulation of E-cadherin protein or mRNA in TW04 cells but moderately increased the β-catenin protein level in TW01 cells and mRNA level in TW06 cells. However, LY294002 substantially restored or increased cell surface E-cadherin and β-catenin in all EGF-treated cell lines, in concordance with the inhibition of cell morphological changes. Moreover, LY294002 significantly blocked EGF-driven cell invasion, correlating with the elevation of membranous E-cadherin and β-catenin levels. In conclusion, EGF-induced epithelial-to-mesenchymal transition may not be only dependent on downregulation of E-cadherin protein/mRNA but also on mislocalization of E-cadherin and β-catenin. The mechanisms involved may be related, at least in part, to the PI3K-Akt pathway.
format	Article
author	Wai, Kien Yip Seow, Heng Fong
spellingShingle	Wai, Kien Yip Seow, Heng Fong Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
author_facet	Wai, Kien Yip Seow, Heng Fong
author_sort	Wai, Kien Yip
title	Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
title_short	Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
title_full	Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
title_fullStr	Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
title_full_unstemmed	Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
title_sort	activation of phosphatidylinositol 3-kinase/akt signaling by egf downregulates membranous e-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.
publisher	Elsevier
publishDate	2012
url	http://psasir.upm.edu.my/id/eprint/24623/1/Activation%20of%20phosphatidylinositol%203.pdf http://psasir.upm.edu.my/id/eprint/24623/ http://www.elsevier.com/
_version_	1643828417015054336
score	13.211869

Activation of phosphatidylinositol 3-kinase/Akt signaling by EGF downregulates membranous E-cadherin and â-catenin and enhances invasion in nasopharyngeal carcinoma cells.

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