Bapx1 mediates transforming growth factor-β- induced epithelial-mesenchymal transition and promotes a malignancy phenotype of gastric cancer cells

Biochem Biophys Res Commun. 2017 Apr 29;486(2):285-292. doi: 10.1016/j.bbrc.2017.03.029. Epub 2017 Mar 14.

Abstract

The homeoprotein Bapx1 is an important regulator of gastroduodenal tract morphogenesis. Here, we investigated how Bapx1 influences gastric cancer (GC) prognosis and elucidated the underlying mechanisms. Bapx1 expression was greater in GC tissues compared to adjacent non-tumor tissues and expression was positively correlated with mortality, lymph node and distance metastasis. Silencing Bapx1 diminished cell invasion/migration and decreased mesenchymal phenotypes. Transforming growth factor-β (TGF-β) induced Bapx1 expression and epithelial-mesenchymal transition (EMT) in GC cells. However, down-regulated Bapx1 reversed TGF-β induced invasion, migration, morphological changes, and EMT. In summary, Bapx1 indicates poor prognosis for GC by promoting tumor migration and invasion via TGF-β-induced EMT.

Keywords: Bapx1; Epithelial-mesenchymal transition; Gastric cancer; TGF-β.

MeSH terms

  • Aged
  • Antigens, CD
  • Cadherins / genetics
  • Cadherins / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / genetics*
  • Carcinoma / mortality
  • Carcinoma / surgery
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Lymphatic Metastasis
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / surgery
  • Survival Analysis
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Vimentin / genetics
  • Vimentin / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Homeodomain Proteins
  • NKX3-2 protein, human
  • RNA, Small Interfering
  • Transcription Factors
  • Transforming Growth Factor beta
  • Vimentin
  • beta Catenin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9