Regulation of cell proliferation by hypoxia-inducible factors

Am J Physiol Cell Physiol. 2015 Dec 15;309(12):C775-82. doi: 10.1152/ajpcell.00279.2015. Epub 2015 Oct 21.


Hypoxia is a physiological cue that impacts diverse physiological processes, including energy metabolism, autophagy, cell motility, angiogenesis, and erythropoiesis. One of the key cell-autonomous effects of hypoxia is as a modulator of cell proliferation. For most cell types, hypoxia induces decreased cell proliferation, since an increased number of cells, with a consequent increase in O2 demand, would only exacerbate hypoxic stress. However, certain cell populations maintain cell proliferation in the face of hypoxia. This is a common pathological hallmark of cancers, but can also serve a physiological function, as in the maintenance of stem cell populations that reside in a hypoxic niche. This review will discuss major molecular mechanisms by which hypoxia regulates cell proliferation in different cell populations, with a particular focus on the role of hypoxia-inducible factors.

Keywords: cell cycle; chaperone-mediated autophagy; cyclin-dependent kinases; hematopoietic stem cells; hypoxia-inducible factor-1; minichromosome maintenance helicase; neural stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia / physiology*
  • Cell Proliferation / physiology*
  • Humans