Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition

Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberran...

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Main Authors:	Kong, Jienan, Di, Chunchan, Piao, Junjie, Sun, Jie, Han, Longzhe, Chen, Liyan, Yan, Guanghai, Lin, Zhenhua
Format:	Online
Language:	English
Published:	Impact Journals LLC 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991407/

id	pubmed-4991407
recordtype	oai_dc
spelling	pubmed-49914072016-09-01 Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition Kong, Jienan Di, Chunchan Piao, Junjie Sun, Jie Han, Longzhe Chen, Liyan Yan, Guanghai Lin, Zhenhua Research Paper Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer. Impact Journals LLC 2016-02-27 /pmc/articles/PMC4991407/ /pubmed/26933912 http://dx.doi.org/10.18632/oncotarget.7779 Text en Copyright: © 2016 Kong et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kong, Jienan Di, Chunchan Piao, Junjie Sun, Jie Han, Longzhe Chen, Liyan Yan, Guanghai Lin, Zhenhua
spellingShingle	Kong, Jienan Di, Chunchan Piao, Junjie Sun, Jie Han, Longzhe Chen, Liyan Yan, Guanghai Lin, Zhenhua Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
author_facet	Kong, Jienan Di, Chunchan Piao, Junjie Sun, Jie Han, Longzhe Chen, Liyan Yan, Guanghai Lin, Zhenhua
author_sort	Kong, Jienan
title	Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
title_short	Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
title_full	Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
title_fullStr	Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
title_full_unstemmed	Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
title_sort	ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition
description	Cervical cancer is the third most common cancer in females worldwide. The treatment options for advanced cervical cancer are limited, leading to high mortality. Ezrin is a membrane-cytoskeleton-binding protein recently reported to act as a tumor promoter, and we previously indicated that the aberrant localization and overexpression of Ezrin could be an independent effective biomarker for prognostic evaluation of cervical cancers. In this study, we identified Ezrin as a regulator of epithelial-mesenchymal transition (EMT) and metastasis in cervical cancer. Ezrin knock-down inhibited anchorage-independent growth, cell migration, and invasion of cervical cancer cell lines in vitro and in vivo. EMT was inhibited in Ezrin-depleted cells, with up-regulation of E-cadherin and Cytokeratin-18 (CK-18) and down-regulation of mesenchymal markers. Ezrin knock-down also induced Akt phosphorylation. These results implicate Ezrin as an EMT regulator and tumor promoter in cervical cancer, and down-regulation of Ezrin suppressed cervical cancer progression, possibly via the phosphoinositide 3-kinase/Akt pathway. Furthermore, the expression pattern of Ezrin protein was closely related with the lymphovascular invasion status of cervical cancer by immunohistochemistry, and the survival analysis revealed that the cervical cancer patients with the perinuclear Ezrin expression pattern had longer survival time than those with the cytoplasmic Ezrin expression pattern. Ezrin thus represents a promising target for the development of novel and effective strategies aimed at preventing the progression of cervical cancer.
publisher	Impact Journals LLC
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991407/
_version_	1613630817265778688

Ezrin contributes to cervical cancer progression through induction of epithelial-mesenchymal transition

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