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

Summary, in 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.

• Author: Alexander Pietras; Kristoffer von Stedingk; David Lindgren; Sven Påhlman; Håkan Axelson
• Department/s: Brain Tumor Biology; Department of Translational Medicine; Division of Translational Cancer Research; Kidney cancer research group; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2011
• Language: English
• Pages: 626-636
• Publication/Series: Molecular Cancer Research
• Volume: 9
• Full text: - 2 MB; Download statistics
• Links: http://www.ncbi.nlm.nih.gov/pubmed/21402725?dopt=Abstract; http://dx.doi.org/10.1158/1541-7786.MCR-10-0508
• Document type: Journal article
• Publisher: American Association for Cancer Research
• Topic: Cancer and Oncology
• Status: Published
• Research group: Brain Tumor Biology; Kidney cancer research group
• ISBN/ISSN/Other: ISSN: 1557-3125