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JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation.

Author:
  • Alexander Pietras
  • Kristoffer von Stedingk
  • David Lindgren
  • Sven Påhlman
  • Håkan Axelson
Publishing year: 2011
Language: English
Pages: 626-636
Publication/Series: Molecular Cancer Research
Volume: 9
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

Several studies have revealed links between hypoxia and activation of Notch in solid tumors. While most reports have focused on icN1 stabilization by direct interaction with HIF proteins, little attention has been given to Notch ligand regulation during hypoxia. Here we show that the Notch ligand JAG2 is transcriptionally activated by hypoxia in a HIF-1α dependent manner. Hypoxic JAG2 induction resulted in elevated Notch activity in tumor cells, as was measured by increased icN1 levels and induction of the Notch target gene HEY1. In primary tumor material, JAG2 expression correlated with vascular development and angiogenesis gene signatures. In line with this, co-culture experiments of endothelial cells with hypoxic breast cancer cells displayed a reduction in number of capillary-like tubes formed upon JAG2 siRNA treatment of the breast cancer cells. Together these results suggest that a hypoxic induction of JAG2 in tumor cells mediates a hypoxia-regulated cross-talk between tumor and endothelial cells.

Keywords

  • Cancer and Oncology

Other

Published
  • Brain Tumor Biology
  • Kidney cancer research group
  • ISSN: 1557-3125
Sven Påhlman
E-mail: sven [dot] pahlman [at] med [dot] lu [dot] se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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