JAG2 induction in hypoxic tumor cells alters Notch signaling and enhances endothelial cell tube formation.
Författare
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.
Avdelning/ar
- Hjärntumörers biologi
- Institutionen för translationell medicin
- Avdelningen för translationell cancerforskning
- Njurcancergruppen
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2011
Språk
Engelska
Sidor
626-636
Publikation/Tidskrift/Serie
Molecular Cancer Research
Volym
9
Fulltext
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association for Cancer Research
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Brain Tumor Biology
- Kidney cancer research group
ISBN/ISSN/Övrigt
- ISSN: 1557-3125