EHF promotes colorectal carcinoma progression by activating TGF-β1 transcription and canonical TGF-β signaling

Cancer Sci. 2020 Jul;111(7):2310-2324. doi: 10.1111/cas.14444. Epub 2020 Jun 10.

Abstract

ETS homologous factor (EHF) plays a critical function in epithelial cell differentiation and proliferation. However, the roles of EHF in cancer remain largely unknown. In the present study, we investigated the expression levels, precise function and mechanism of EHF in colorectal carcinoma (CRC). We observed significantly elevated EHF expression in CRC cell lines and tissues. EHF overexpression correlated positively with poor differentiation, advanced T stage, and shorter overall survival of CRC patients. Function experiments revealed that EHF overexpression promoted CRC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EHF could directly upregulate transforming growth factor β1 (TGF-β1) expression at the transcription level, thereby activating canonical TGF-β signaling. Our findings provide novel insights into the mechanisms of EHF in tumorigenesis, invasion, and metastasis of CRC, which may help to provide new therapeutic targets for CRC intervention.

Keywords: EHF; TGF-β signaling; colorectal carcinoma; proliferation and migration; transcription factor.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Middle Aged
  • Models, Biological
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Protein Transport
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation*
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism*
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • EHF protein, human
  • Transcription Factors
  • Transforming Growth Factor beta1