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

Pietras, AlexanderLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Hjärntumörers biologi,Forskargrupper vid Lunds universitet,Department of Translational Medicine,Faculty of Medicine,Brain Tumor Biology,Lund University Research Groups,Skåne University Hospital (författare)

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.

von Stedingk, KristofferLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine(Swepub:lu)med-kvt (författare)
Lindgren, DavidLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Njurcancergruppen,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Kidney cancer research group,Lund University Research Groups(Swepub:lu)kgen-dli (författare)
Påhlman, SvenLund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine,Skåne University Hospital(Swepub:lu)molm-spa (författare)
Axelson, HåkanLund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Njurcancergruppen,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Kidney cancer research group,Lund University Research Groups(Swepub:lu)molm-hax (författare)
Institutionen för translationell medicinMedicinska fakulteten (creator_code:org_t)

Av författaren/redakt...: Pietras, Alexand ...; von Stedingk, Kr ...; Lindgren, David; Påhlman, Sven; Axelson, Håkan

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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