MTA1 promotes the invasion and migration of oral squamous carcinoma by inducing epithelial-mesenchymal transition via the hedgehog signaling pathway

Exp Cell Res. 2019 Sep 1;382(1):111450. doi: 10.1016/j.yexcr.2019.05.031. Epub 2019 May 29.

Abstract

The metastasis-associated gene 1 (MTA1) has previously been recognized as an oncogene in many tumors, and aberrant MTA1 expression has been related to invasion and migration; however, its role and underlying molecular mechanism in oral squamous carcinoma (OSCC) remain largely unexplored. In this work, we determined the expression of MTA1 in OSCC tissues and cell lines. The effect of MTA1 on metastasis and the role of MTA1 in the epithelial-to-mesenchymal transition (EMT) of OSCC cells were evaluated by assays both in vitro and in vivo. We also identified the key Hedgehog signaling pathway-related protein involved in the MTA1-induced EMT. We found that MTA1 expression was upregulated and positively related to the metastasis in OSCC tissues and cell lines. MTA1 overexpression promoted OSCC invasion, migration, and induced EMT, while its silencing had the opposite effect both in vitro and in vivo. Additionally, our data further revealed the relevant molecular mechanism, Hedgehog(Hh) signaling pathway contributed to the effect of MTA1 on the aggressive phenotypes of OSCC cells.These findings indicate that MTA1 enhances OSCC cells invasion and migration by inducing EMT via the Hedgehog signaling pathway, which suggests MTA1 may be an effective anti-OSCC therapeutic target.

Keywords: Epithelial-to-mesenchymal transition; Hedgehog signaling pathway; Invasion and migration; MTA1; Oral squamous carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Carcinoma, Squamous Cell / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Hedgehog Proteins / physiology*
  • Heterografts
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Recombinant Proteins / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Signal Transduction / physiology*
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Up-Regulation
  • Zinc Finger Protein GLI1 / physiology*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • GLI1 protein, human
  • Hedgehog Proteins
  • MTA1 protein, human
  • Neoplasm Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Trans-Activators
  • Zinc Finger Protein GLI1