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DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer

BACKGROUND: Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a pro...

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Autores principales: Chen, Xianliang, Guan, Xiaoying, Zhang, Huiyu, Xie, Xiaobin, Wang, Hongyan, Long, Jie, Cai, Tonghui, Li, Shuhua, Liu, Zhen, Zhang, Yajie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307741/
https://www.ncbi.nlm.nih.gov/pubmed/25609022
http://dx.doi.org/10.1186/s13046-014-0117-2
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author Chen, Xianliang
Guan, Xiaoying
Zhang, Huiyu
Xie, Xiaobin
Wang, Hongyan
Long, Jie
Cai, Tonghui
Li, Shuhua
Liu, Zhen
Zhang, Yajie
author_facet Chen, Xianliang
Guan, Xiaoying
Zhang, Huiyu
Xie, Xiaobin
Wang, Hongyan
Long, Jie
Cai, Tonghui
Li, Shuhua
Liu, Zhen
Zhang, Yajie
author_sort Chen, Xianliang
collection PubMed
description BACKGROUND: Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein belongs to the membrane-associated cytoskeleton protein 4.1 family, as an efficient suppressor of EMT in lung cancer. METHODS: The relationship between DAL-1 and EMT markers were analyzed by using immunohistochemistry in the clinical lung cancer tissues. Quantitative real-time PCR and western blot were used to characterize the expression of the EMT indicator mRNAs and proteins in DAL-1 overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co-immunoprecipitation. RESULTS: DAL-1 levels were strongly reduced even lost in lymph node metastasis and advanced pathological stage of human lung carcinomas. Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E-cadherin, β-catenin Vimentin and N-cadherin expression, meanwhile changed the morphological shape of lung cancer cells, and whereas silencing DAL-1 had an opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated its expression that could be the reason for impairing EMT and decreasing cell migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding protein. CONCLUSIONS: These results suggest that tumor suppressor DAL-1 could also attenuate EMT and be important for tumor metastasis in the early transformation process in lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-014-0117-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-43077412015-01-28 DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer Chen, Xianliang Guan, Xiaoying Zhang, Huiyu Xie, Xiaobin Wang, Hongyan Long, Jie Cai, Tonghui Li, Shuhua Liu, Zhen Zhang, Yajie J Exp Clin Cancer Res Research BACKGROUND: Epithelial-to mesenchymal transition (EMT) involves in metastasis, causing loss of epithelial polarity. Metastasis is the major cause of carcinoma-induced death, but mechanisms are poorly understood. Here we identify differentially expressed in adenocarcinoma of the lung-1 (DAL-1), a protein belongs to the membrane-associated cytoskeleton protein 4.1 family, as an efficient suppressor of EMT in lung cancer. METHODS: The relationship between DAL-1 and EMT markers were analyzed by using immunohistochemistry in the clinical lung cancer tissues. Quantitative real-time PCR and western blot were used to characterize the expression of the EMT indicator mRNAs and proteins in DAL-1 overexpressed or knockdown cells. DAL-1 combined proteins were assessed by co-immunoprecipitation. RESULTS: DAL-1 levels were strongly reduced even lost in lymph node metastasis and advanced pathological stage of human lung carcinomas. Overexpression of DAL-1 altered the expression of numerous EMT markers, such as E-cadherin, β-catenin Vimentin and N-cadherin expression, meanwhile changed the morphological shape of lung cancer cells, and whereas silencing DAL-1 had an opposite effect. DAL-1 directly combined with E-cadherin promoter and regulated its expression that could be the reason for impairing EMT and decreasing cell migration and invasion. Strikingly, HSPA5 was found as DAL-1 direct binding protein. CONCLUSIONS: These results suggest that tumor suppressor DAL-1 could also attenuate EMT and be important for tumor metastasis in the early transformation process in lung cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-014-0117-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-22 /pmc/articles/PMC4307741/ /pubmed/25609022 http://dx.doi.org/10.1186/s13046-014-0117-2 Text en © Chen et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Chen, Xianliang
Guan, Xiaoying
Zhang, Huiyu
Xie, Xiaobin
Wang, Hongyan
Long, Jie
Cai, Tonghui
Li, Shuhua
Liu, Zhen
Zhang, Yajie
DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title_full DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title_fullStr DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title_full_unstemmed DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title_short DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer
title_sort dal-1 attenuates epithelial-to mesenchymal transition in lung cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4307741/
https://www.ncbi.nlm.nih.gov/pubmed/25609022
http://dx.doi.org/10.1186/s13046-014-0117-2
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