c-Myc enhances colon cancer cell-mediated angiogenesis through the regulation of HIF-1α

Biochem Biophys Res Commun. 2013 Jan 11;430(2):505-11. doi: 10.1016/j.bbrc.2012.12.006. Epub 2012 Dec 10.

Abstract

Angiogenesis plays a pivotal role in tumor growth. The hypoxia-inducible factor 1, α subunit (HIF-1α)/vascular endothelial growth factor pathway is the most important pathway for regulating angiogenesis in the tumor microenvironment. c-Myc is an important oncogene that has many biological functions. In this study, we investigated the role of c-Myc in tumor angiogenesis. We found that the overexpression of c-Myc in colon cancer cells could promote the expression of HIF-1α and that of vascular endothelial growth factor. Moreover, we found that c-Myc regulated HIF-1α at the post-transcriptional level. The results revealed c-Myc-dependent regulation of HIF-1α instead of HIF-1α-dependent c-Myc regulation for the first time. They also showed that c-Myc was essential to regulate colon cancer cell-mediated angiogenesis and contributed to tumor growth. This research provides the theoretical basis for clinical trials of new therapeutic targets of c-Myc and HIF-1α in colon cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / pathology
  • Humans
  • Hypoxia-Inducible Factor 1 / biosynthesis*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / metabolism*
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Vascular Endothelial Growth Factor A / biosynthesis

Substances

  • Hypoxia-Inducible Factor 1
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A