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Raising the bar: how HIF-1 helps determine tumor radiosensitivity.

Publication ,  Journal Article
Moeller, BJ; Dewhirst, MW
Published in: Cell Cycle
September 2004

Through a poorly understood mechanism, tumors respond to radiation by secreting cytokines which inhibit endothelial cell apoptosis, thereby limiting treatment response by minimizing vessel damage. We have recently discovered that this pathway is governed by a major angiogenesis regulator, hypoxia-inducible factor-1 (HIF-1). We uncovered dual mechanisms initiated by radiation that both simultaneously lead to HIF-1 activation: (1) reoxygenation-induced stabilization of the HIF-1 dimer through free radical intermediates, and (2) reoxygenation-mediated depolymerization of hypoxia-induced translational suppressors known as stress granules. These findings have implications both for understanding the basic science of hypoxic signaling in tumors, and for discovering novel methods of enhancing conventional anti-tumor therapeutics in the clinic. In this article, we will highlight the apparent importance of free radical species in protecting tumor vasculature, stress granules in regulating hypoxic gene expression, and HIF-1 in regulating tumor sensitivity to ionizing radiation. The potential therapeutic utility of these findings will also be explored, with emphasis placed on putative targets in these pathways which may enhance tumor radiotherapy.

Duke Scholars

Published In

Cell Cycle

EISSN

1551-4005

Publication Date

September 2004

Volume

3

Issue

9

Start / End Page

1107 / 1110

Location

United States

Related Subject Headings

  • Radiation Tolerance
  • Oxidative Stress
  • Neovascularization, Pathologic
  • Neoplasms
  • Hypoxia-Inducible Factor 1
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Free Radicals
  • Developmental Biology
  • Cytoplasmic Granules
 

Citation

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Moeller, B. J., & Dewhirst, M. W. (2004). Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle, 3(9), 1107–1110.
Moeller, Benjamin J., and Mark W. Dewhirst. “Raising the bar: how HIF-1 helps determine tumor radiosensitivity.Cell Cycle 3, no. 9 (September 2004): 1107–10.
Moeller BJ, Dewhirst MW. Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle. 2004 Sep;3(9):1107–10.
Moeller, Benjamin J., and Mark W. Dewhirst. “Raising the bar: how HIF-1 helps determine tumor radiosensitivity.Cell Cycle, vol. 3, no. 9, Sept. 2004, pp. 1107–10.
Moeller BJ, Dewhirst MW. Raising the bar: how HIF-1 helps determine tumor radiosensitivity. Cell Cycle. 2004 Sep;3(9):1107–1110.

Published In

Cell Cycle

EISSN

1551-4005

Publication Date

September 2004

Volume

3

Issue

9

Start / End Page

1107 / 1110

Location

United States

Related Subject Headings

  • Radiation Tolerance
  • Oxidative Stress
  • Neovascularization, Pathologic
  • Neoplasms
  • Hypoxia-Inducible Factor 1
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Free Radicals
  • Developmental Biology
  • Cytoplasmic Granules