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Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells

Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadh...

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Autores principales: Wang, Hongyan, Fan, Liangsheng, Wei, Juncheng, Weng, Yanjie, Zhou, Li, Shi, Ying, Zhou, Wenjuan, Ma, Ding, Wang, Changyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515600/
https://www.ncbi.nlm.nih.gov/pubmed/23227138
http://dx.doi.org/10.1371/journal.pone.0046888
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author Wang, Hongyan
Fan, Liangsheng
Wei, Juncheng
Weng, Yanjie
Zhou, Li
Shi, Ying
Zhou, Wenjuan
Ma, Ding
Wang, Changyu
author_facet Wang, Hongyan
Fan, Liangsheng
Wei, Juncheng
Weng, Yanjie
Zhou, Li
Shi, Ying
Zhou, Wenjuan
Ma, Ding
Wang, Changyu
author_sort Wang, Hongyan
collection PubMed
description Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis.
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spelling pubmed-35156002012-12-07 Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells Wang, Hongyan Fan, Liangsheng Wei, Juncheng Weng, Yanjie Zhou, Li Shi, Ying Zhou, Wenjuan Ma, Ding Wang, Changyu PLoS One Research Article Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis. Public Library of Science 2012-12-05 /pmc/articles/PMC3515600/ /pubmed/23227138 http://dx.doi.org/10.1371/journal.pone.0046888 Text en © 2012 Wang et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Wang, Hongyan
Fan, Liangsheng
Wei, Juncheng
Weng, Yanjie
Zhou, Li
Shi, Ying
Zhou, Wenjuan
Ma, Ding
Wang, Changyu
Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title_full Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title_fullStr Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title_full_unstemmed Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title_short Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
title_sort akt mediates metastasis-associated gene 1 (mta1) regulating the expression of e-cadherin and promoting the invasiveness of prostate cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515600/
https://www.ncbi.nlm.nih.gov/pubmed/23227138
http://dx.doi.org/10.1371/journal.pone.0046888
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