MTA1 promotes metastasis of MPM via suppression of E-cadherin

J Exp Clin Cancer Res. 2015 Dec 21:34:151. doi: 10.1186/s13046-015-0269-8.

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.

MeSH terms

  • Adult
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Cadherins / biosynthesis*
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Histone Deacetylases / biosynthesis*
  • Histone Deacetylases / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Mesothelioma / genetics*
  • Mesothelioma, Malignant
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Small Interfering / genetics
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics
  • Survival Analysis
  • Trans-Activators

Substances

  • Biomarkers, Tumor
  • Cadherins
  • MTA1 protein, human
  • RNA, Small Interfering
  • Repressor Proteins
  • Trans-Activators
  • Histone Deacetylases