TRIM32 promotes cell proliferation and invasion by activating β-catenin signalling in gastric cancer

J Cell Mol Med. 2018 Oct;22(10):5020-5028. doi: 10.1111/jcmm.13784. Epub 2018 Aug 5.

Abstract

The tripartite motif (TRIM) family comprises more than 70 members involved in the regulation of many cellular pathways. TRIM32 acts as an E3 ubiquitin ligase and has been reported to participate in many human cancers. Here, we aimed to investigate the role of TRIM32 in gastric cancer (GC) and the clinical implications. High expression of TRIM32 was observed in GC tissues and cell lines, and was significantly associated with poor prognosis. Knockdown TRIM32 expression remarkably suppressed the proliferation, migration, and invasion of GC cells in vitro and tumour growth in vivo, whereas overexpression of TRIM32 yielded the opposite results. Western blotting and quantitative reverse-transcription PCR (qRT-PCR) analyses revealed that up-regulation of TRIM32 significantly enhanced expression of β-catenin protein and of its downstream targets TCF1, cyclin D1, Axin2 and MMP7 mRNAs. Moreover, we found that the mechanism behind the TRIM32-promoted GC progression was related to the β-catenin signalling pathway. Collectively, these data suggest that TRIM32 promotes GC cell proliferation, migration, and invasion by activating the β-catenin signalling pathway.

Keywords: TRIM32; gastric cancer; invasion; proliferation; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axin Protein / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cyclin D1 / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 1-alpha / genetics
  • Humans
  • Male
  • Matrix Metalloproteinase 7 / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transcription Factors / genetics*
  • Tripartite Motif Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics*
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics*

Substances

  • AXIN2 protein, human
  • Axin Protein
  • CTNNB1 protein, human
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Transcription Factors
  • Tripartite Motif Proteins
  • beta Catenin
  • Cyclin D1
  • TRIM32 protein, human
  • Ubiquitin-Protein Ligases
  • MMP7 protein, human
  • Matrix Metalloproteinase 7