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Published in: Journal of Experimental & Clinical Cancer Research 1/2015

Open Access 01-12-2015 | Research

MTA1 promotes metastasis of MPM via suppression of E-cadherin

Authors: Caihua Xu, Fei Hua, Yihuan Chen, Haoyue Huang, Wenxue Ye, Yunsheng Yu, Zhenya Shen

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

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Abstract

Background

Metastasis-associated gene 1(MTA1) has been identified as an oncogene in many tumors, and aberrant MTA1 expression has been linked to carcinogenesis and metastasis. We aim to investigate the mechanism of MTA1 and metastasis in malignant pleural mesothelioma (MPM).

Methods

Real-time polymerase chain reaction (PCR) and immunohistochemical staining were employed to detect MTA1 and E-cadherin expression in MPM tissues and corresponding adjacent tissues. Stable clone with knock-down of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Wound-healing assay, transwell assay and PCR array were carried out for detecting invasion and migration of MPM cells. Luciferase reporter assay was performed to validate the effect of MTA1 on E-cadherin.

Results

MTA1 expression is up-regulated in MPM and shown a negative correlation with E-cadherin expression. MTA1 could enhance the invasion and migration of MPM cells via suppressing the expression of E-cadherin. MTA1 overexpression is associated with pathology, metastasis and survival rate of MPM patients.

Conclusions

MTA1 plays an important role in Epithelial-to-mesenchymal transition (EMT) to promote metastasis via suppressing E-cadherin expression, resulting in a poor prognosis in MPM. MTA1 is a novel biomarker and indicative of a poor prognosis in MPM patients.
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Literature
1.
go back to reference Tsao AS, Wistuba I, Roth JA, Kindler HL. Malignant pleural mesothelioma. J Clin Oncol. 2009;27:2081–90.PubMedCrossRef Tsao AS, Wistuba I, Roth JA, Kindler HL. Malignant pleural mesothelioma. J Clin Oncol. 2009;27:2081–90.PubMedCrossRef
2.
go back to reference Carbonelli C, Rapicetta C, Cesario A. Surgery and survival of patients with diagnosis of malignant pleural mesothelioma. J Thorac Oncol. 2015;10:e92–3.PubMedCrossRef Carbonelli C, Rapicetta C, Cesario A. Surgery and survival of patients with diagnosis of malignant pleural mesothelioma. J Thorac Oncol. 2015;10:e92–3.PubMedCrossRef
3.
go back to reference Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009;26:215–27.PubMedCrossRef Toh Y, Nicolson GL. The role of the MTA family and their encoded proteins in human cancers: molecular functions and clinical implications. Clin Exp Metastasis. 2009;26:215–27.PubMedCrossRef
4.
go back to reference Manavathi B, Kumar R. Metastasis tumor antigens, an emerging family of multifaceted master coregulators. J Biol Chem. 2007;282:1529–33.PubMedCrossRef Manavathi B, Kumar R. Metastasis tumor antigens, an emerging family of multifaceted master coregulators. J Biol Chem. 2007;282:1529–33.PubMedCrossRef
5.
go back to reference Balasenthil S, Broaddus RR, Kumar R. Expression of metastasis-associated protein 1 (MTA1) in benign endometrium and endometrial adenocarcinomas. Hum Pathol. 2006;37:656–61.PubMedCrossRef Balasenthil S, Broaddus RR, Kumar R. Expression of metastasis-associated protein 1 (MTA1) in benign endometrium and endometrial adenocarcinomas. Hum Pathol. 2006;37:656–61.PubMedCrossRef
6.
go back to reference Kidd M, Modlin IM, Mane SM, Camp RL, Eick G, Latich I. The role of genetic markers--NAP1L1, MAGE-D2, and MTA1--in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol. 2006;13:253–62.PubMedCrossRef Kidd M, Modlin IM, Mane SM, Camp RL, Eick G, Latich I. The role of genetic markers--NAP1L1, MAGE-D2, and MTA1--in defining small-intestinal carcinoid neoplasia. Ann Surg Oncol. 2006;13:253–62.PubMedCrossRef
7.
go back to reference Giannini R, Cavallini A. Expression analysis of a subset of coregulators and three nuclear receptors in human colorectal carcinoma. Anticancer Res. 2005;25:4287–92.PubMed Giannini R, Cavallini A. Expression analysis of a subset of coregulators and three nuclear receptors in human colorectal carcinoma. Anticancer Res. 2005;25:4287–92.PubMed
8.
go back to reference Hamatsu T, Rikimaru T, Yamashita Y, Aishima S, Tanaka S, Shirabe K, et al. The role of MTA1 gene expression in human hepatocellular carcinoma. Oncol Rep. 2003;10:599–604.PubMed Hamatsu T, Rikimaru T, Yamashita Y, Aishima S, Tanaka S, Shirabe K, et al. The role of MTA1 gene expression in human hepatocellular carcinoma. Oncol Rep. 2003;10:599–604.PubMed
9.
go back to reference Zhu X, Guo Y, Li X, Ding Y, Chen L. Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer. J Thorac Oncol. 2010;5:1159–66.PubMedCrossRef Zhu X, Guo Y, Li X, Ding Y, Chen L. Metastasis-associated protein 1 nuclear expression is associated with tumor progression and clinical outcome in patients with non-small cell lung cancer. J Thorac Oncol. 2010;5:1159–66.PubMedCrossRef
10.
go back to reference Li Y, Chao Y, Fang Y, Wang J, Wang M, Zhang H, et al. MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b. J Exp Clin Cancer Res. 2013;32:33.PubMedPubMedCentralCrossRef Li Y, Chao Y, Fang Y, Wang J, Wang M, Zhang H, et al. MTA1 promotes the invasion and migration of non-small cell lung cancer cells by downregulating miR-125b. J Exp Clin Cancer Res. 2013;32:33.PubMedPubMedCentralCrossRef
11.
go back to reference Martinez-Estrada OM, Lettice LA, Essafi A, Guadix JA, Slight J, Velecela V, et al. Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet. 2010;42:89–93.PubMedPubMedCentralCrossRef Martinez-Estrada OM, Lettice LA, Essafi A, Guadix JA, Slight J, Velecela V, et al. Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet. 2010;42:89–93.PubMedPubMedCentralCrossRef
12.
go back to reference Pakala SB, Singh K, Reddy SD, Ohshiro K, Li DQ, Mishra L, et al. TGF-beta1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells. Oncogene. 2011;30:2230–41.PubMedPubMedCentralCrossRef Pakala SB, Singh K, Reddy SD, Ohshiro K, Li DQ, Mishra L, et al. TGF-beta1 signaling targets metastasis-associated protein 1, a new effector in epithelial cells. Oncogene. 2011;30:2230–41.PubMedPubMedCentralCrossRef
13.
go back to reference Deng L, Yang H, Tang J, Lin Z, Yin A, Gao Y, et al. Inhibition of MTA1 by ERalpha contributes to protection hepatocellular carcinoma from tumor proliferation and metastasis. J Exp Clin Cancer Res. 2015;34:128.PubMedPubMedCentralCrossRef Deng L, Yang H, Tang J, Lin Z, Yin A, Gao Y, et al. Inhibition of MTA1 by ERalpha contributes to protection hepatocellular carcinoma from tumor proliferation and metastasis. J Exp Clin Cancer Res. 2015;34:128.PubMedPubMedCentralCrossRef
14.
go back to reference Song Q, Zhang H, Wang M, Song W, Ying M, Fang Y, et al. MTA1 promotes nasopharyngeal carcinoma growth in vitro and in vivo. J Exp Clin Cancer Res. 2013;32:54.PubMedPubMedCentralCrossRef Song Q, Zhang H, Wang M, Song W, Ying M, Fang Y, et al. MTA1 promotes nasopharyngeal carcinoma growth in vitro and in vivo. J Exp Clin Cancer Res. 2013;32:54.PubMedPubMedCentralCrossRef
15.
go back to reference Kumar P, Kratzke RA. Molecular prognostic markers in malignant mesothelioma. Lung Cancer. 2005;49 Suppl 1:S53–60.PubMedCrossRef Kumar P, Kratzke RA. Molecular prognostic markers in malignant mesothelioma. Lung Cancer. 2005;49 Suppl 1:S53–60.PubMedCrossRef
16.
go back to reference Toh Y, Ohga T, Endo K, Adachi E, Kusumoto H, Haraguchi M, et al. Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. Int J Cancer. 2004;110:362–7.PubMedCrossRef Toh Y, Ohga T, Endo K, Adachi E, Kusumoto H, Haraguchi M, et al. Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. Int J Cancer. 2004;110:362–7.PubMedCrossRef
17.
go back to reference Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, et al. The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004;64:825–9.PubMedCrossRef Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, et al. The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004;64:825–9.PubMedCrossRef
18.
go back to reference Mahoney MG, Simpson A, Jost M, Noe M, Kari C, Pepe D, et al. Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene. 2002;21:2161–70.PubMedCrossRef Mahoney MG, Simpson A, Jost M, Noe M, Kari C, Pepe D, et al. Metastasis-associated protein (MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene. 2002;21:2161–70.PubMedCrossRef
19.
go back to reference Hofer MD, Menke A, Genze F, Gierschik P, Giehl K. Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer. 2004;90:455–62.PubMedPubMedCentralCrossRef Hofer MD, Menke A, Genze F, Gierschik P, Giehl K. Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells. Br J Cancer. 2004;90:455–62.PubMedPubMedCentralCrossRef
20.
go back to reference Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, et al. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001;3:30–7.PubMedCrossRef Mazumdar A, Wang RA, Mishra SK, Adam L, Bagheri-Yarmand R, Mandal M, et al. Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor. Nat Cell Biol. 2001;3:30–7.PubMedCrossRef
22.
go back to reference Li DQ, Pakala SB, Reddy SD, Ohshiro K, Peng SH, Lian Y, et al. Revelation of p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway. J Biol Chem. 2010;285:10044–52.PubMedPubMedCentralCrossRef Li DQ, Pakala SB, Reddy SD, Ohshiro K, Peng SH, Lian Y, et al. Revelation of p53-independent function of MTA1 in DNA damage response via modulation of the p21 WAF1-proliferating cell nuclear antigen pathway. J Biol Chem. 2010;285:10044–52.PubMedPubMedCentralCrossRef
23.
go back to reference Gururaj AE, Singh RR, Rayala SK, Holm C, den Hollander P, Zhang H, et al. MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proc Natl Acad Sci U S A. 2006;103:6670–5.PubMedPubMedCentralCrossRef Gururaj AE, Singh RR, Rayala SK, Holm C, den Hollander P, Zhang H, et al. MTA1, a transcriptional activator of breast cancer amplified sequence 3. Proc Natl Acad Sci U S A. 2006;103:6670–5.PubMedPubMedCentralCrossRef
24.
go back to reference Balasenthil S, Gururaj AE, Talukder AH, Bagheri-Yarmand R, Arrington T, Haas BJ, et al. Identification of Pax5 as a target of MTA1 in B-cell lymphomas. Cancer Res. 2007;67:7132–8.PubMedCrossRef Balasenthil S, Gururaj AE, Talukder AH, Bagheri-Yarmand R, Arrington T, Haas BJ, et al. Identification of Pax5 as a target of MTA1 in B-cell lymphomas. Cancer Res. 2007;67:7132–8.PubMedCrossRef
25.
go back to reference Jiang Q, Zhang H, Zhang P. ShRNA-mediated gene silencing of MTA1 influenced on protein expression of ER alpha, MMP-9, CyclinD1 and invasiveness, proliferation in breast cancer cell lines MDA-MB-231 and MCF-7 in vitro. J Exp Clin Cancer Res. 2011;30:60.PubMedPubMedCentralCrossRef Jiang Q, Zhang H, Zhang P. ShRNA-mediated gene silencing of MTA1 influenced on protein expression of ER alpha, MMP-9, CyclinD1 and invasiveness, proliferation in breast cancer cell lines MDA-MB-231 and MCF-7 in vitro. J Exp Clin Cancer Res. 2011;30:60.PubMedPubMedCentralCrossRef
26.
go back to reference Rao Y, Wang H, Fan L, Chen G. Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/beta-catenin complex. J Huazhong Univ Sci Technolog Med Sci. 2011;31:1–9.PubMedCrossRef Rao Y, Wang H, Fan L, Chen G. Silencing MTA1 by RNAi reverses adhesion, migration and invasiveness of cervical cancer cells (SiHa) via altered expression of p53, and E-cadherin/beta-catenin complex. J Huazhong Univ Sci Technolog Med Sci. 2011;31:1–9.PubMedCrossRef
27.
go back to reference Zhang KJ, Wang DS, Zhang SY, Jiao XL, Li CW, Wang XS, et al. The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma. J Exp Clin Cancer Res. 2010;29:88.PubMedPubMedCentralCrossRef Zhang KJ, Wang DS, Zhang SY, Jiao XL, Li CW, Wang XS, et al. The E-cadherin repressor slug and progression of human extrahepatic hilar cholangiocarcinoma. J Exp Clin Cancer Res. 2010;29:88.PubMedPubMedCentralCrossRef
28.
go back to reference Weng W, Yin J, Zhang Y, Qiu J, Wang X. Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin. Int J Oncol. 2014;44:812–8.PubMed Weng W, Yin J, Zhang Y, Qiu J, Wang X. Metastasis-associated protein 1 promotes tumor invasion by downregulation of E-cadherin. Int J Oncol. 2014;44:812–8.PubMed
29.
go back to reference Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119:1438–49.PubMedPubMedCentralCrossRef Acloque H, Adams MS, Fishwick K, Bronner-Fraser M, Nieto MA. Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J Clin Invest. 2009;119:1438–49.PubMedPubMedCentralCrossRef
30.
go back to reference Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.PubMedCrossRef Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.PubMedCrossRef
31.
go back to reference Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75–90.PubMed Voulgari A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta. 2009;1796:75–90.PubMed
32.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedPubMedCentralCrossRef Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedPubMedCentralCrossRef
Metadata
Title
MTA1 promotes metastasis of MPM via suppression of E-cadherin
Authors
Caihua Xu
Fei Hua
Yihuan Chen
Haoyue Huang
Wenxue Ye
Yunsheng Yu
Zhenya Shen
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-015-0269-8

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