Hypoxia inducible factor-1α: Its role in colorectal carcinogenesis and metastasis

Cancer Lett. 2015 Sep 28;366(1):11-8. doi: 10.1016/j.canlet.2015.06.005. Epub 2015 Jun 24.

Abstract

Tumor growth creates a hypoxic microenvironment, which promotes angiogenesis and aggressive tumor growth and invasion. HIF1α is a central molecule involved in mediating these effects of hypoxia. In colorectal cancer (CRC), hypoxia stabilizes the transcription factor HIF1α, leading to the expression of genes that are involved in tumor vascularization, metastasis/migration, cell survival and chemo-resistance. Therefore, HIF1α is a rational target for the development of new therapeutics for CRC. This article reviews the central role of HIF1α in CRC angiogenesis, metastasis, and progression as well as the strategies to target HIF1α stabilization.

Keywords: Colorectal cancer; HIF1α; Metastasis; Stemness; Tumor resistance.

Publication types

  • Review

MeSH terms

  • Colorectal Neoplasms / etiology*
  • Colorectal Neoplasms / pathology*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / chemistry
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology*
  • MicroRNAs / physiology
  • Neoplasm Metastasis
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / physiology
  • Protein Stability
  • Reactive Oxygen Species / metabolism
  • Receptors, CXCR4 / physiology
  • beta Catenin / physiology

Substances

  • CTNNB1 protein, human
  • CXCR4 protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Reactive Oxygen Species
  • Receptors, CXCR4
  • beta Catenin