The histone deacetylase HDAC1 activates HIF1α/VEGFA signal pathway in colorectal cancer

Gene. 2020 Sep 5:754:144851. doi: 10.1016/j.gene.2020.144851. Epub 2020 Jun 7.

Abstract

Tumor angiogenesis is a common feature of rapidly growing solid tumors, accelerated by tumor hypoxia. It is associated with subsequent metastasis, progression, poor prognosis, and aggressive phenotype in many types of cancer. The hypoxia-inducible factors/vascular endothelial growth factor 1(HIF1/VEGF) signal pathway plays an important role in tumor angiogenesis. Proteasome-mediated ubiquitin degradation pathway is one of the most important processes involved in regulating the level of cellular HIF-1α. Our study revealed that Histone Deacetylase 1 (HDAC1) directly inhibits the ubiquitination of HIF1α. Additionally, HDAC1 activates HIF1α/VEGFA signaling pathway, promoting s tumor angiogenesis. These findings have enhanced our understanding of the molecular mechanisms of colorectal (CRC) tumor angiogenesis. HDAC1/HIF1α/VEGFA signaling pathway may provide a novel therapeutic window for CRC.

Keywords: Colorectal cancer; HDAC1; HIF1α; Tumor angiogenesis.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Histone Deacetylase 1 / genetics
  • Histone Deacetylase 1 / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Prognosis
  • Signal Transduction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • HDAC1 protein, human
  • Histone Deacetylase 1