Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. A...

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Main Authors: Meng, X, Kong, D-H, Li, N, Zong, Z-H, Liu, B-Q, Du, Z-X, Guan, Y, Cao, L, Wang, H-Q
Format: Online
Language:English
Published: Nature Publishing Group 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944249/
id pubmed-3944249
recordtype oai_dc
spelling pubmed-39442492014-03-06 Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation Meng, X Kong, D-H Li, N Zong, Z-H Liu, B-Q Du, Z-X Guan, Y Cao, L Wang, H-Q Original Article The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis. Nature Publishing Group 2014-02 2014-02-27 /pmc/articles/PMC3944249/ /pubmed/24577090 http://dx.doi.org/10.1038/cddis.2014.32 Text en Copyright © 2014 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
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 Meng, X
Kong, D-H
Li, N
Zong, Z-H
Liu, B-Q
Du, Z-X
Guan, Y
Cao, L
Wang, H-Q
spellingShingle Meng, X
Kong, D-H
Li, N
Zong, Z-H
Liu, B-Q
Du, Z-X
Guan, Y
Cao, L
Wang, H-Q
Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
author_facet Meng, X
Kong, D-H
Li, N
Zong, Z-H
Liu, B-Q
Du, Z-X
Guan, Y
Cao, L
Wang, H-Q
author_sort Meng, X
title Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
title_short Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
title_full Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
title_fullStr Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
title_full_unstemmed Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation
title_sort knockdown of bag3 induces epithelial–mesenchymal transition in thyroid cancer cells through zeb1 activation
description The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.
publisher Nature Publishing Group
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944249/
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