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MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer
BACKGROUND: Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients’ poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduc...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690245/ https://www.ncbi.nlm.nih.gov/pubmed/26698569 http://dx.doi.org/10.1186/s13046-015-0263-1 |
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author | Zhou, Ning Wang, Haijuan Liu, Hongxu Xue, Hongsheng Lin, Feng Meng, Xiting Liang, Ailing Zhao, Zhilong Liu, YongJun Qian, Haili |
author_facet | Zhou, Ning Wang, Haijuan Liu, Hongxu Xue, Hongsheng Lin, Feng Meng, Xiting Liang, Ailing Zhao, Zhilong Liu, YongJun Qian, Haili |
author_sort | Zhou, Ning |
collection | PubMed |
description | BACKGROUND: Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients’ poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients’ prognosis. METHODS: We checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software. RESULTS: MTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What’s more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival. CONCLUSIONS: We revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma. |
format | Online Article Text |
id | pubmed-4690245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46902452015-12-25 MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer Zhou, Ning Wang, Haijuan Liu, Hongxu Xue, Hongsheng Lin, Feng Meng, Xiting Liang, Ailing Zhao, Zhilong Liu, YongJun Qian, Haili J Exp Clin Cancer Res Research BACKGROUND: Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients’ poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients’ prognosis. METHODS: We checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software. RESULTS: MTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What’s more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival. CONCLUSIONS: We revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma. BioMed Central 2015-12-23 /pmc/articles/PMC4690245/ /pubmed/26698569 http://dx.doi.org/10.1186/s13046-015-0263-1 Text en © Zhou et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Zhou, Ning Wang, Haijuan Liu, Hongxu Xue, Hongsheng Lin, Feng Meng, Xiting Liang, Ailing Zhao, Zhilong Liu, YongJun Qian, Haili MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title | MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title_full | MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title_fullStr | MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title_full_unstemmed | MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title_short | MTA1-upregulated EpCAM is associated with metastatic behaviors and poor prognosis in lung cancer |
title_sort | mta1-upregulated epcam is associated with metastatic behaviors and poor prognosis in lung cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690245/ https://www.ncbi.nlm.nih.gov/pubmed/26698569 http://dx.doi.org/10.1186/s13046-015-0263-1 |
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