Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Angiogenesis is a coordinated process tightly regulated by the balance between Delta-like-4 (DLL4) and Jagged-1 (JAG1) in endothelial cells. Here we show that galectin-3 (gal-3), a glycan-binding protein secreted by cancer cells under hypoxic conditions, triggers sprouting angiogenesis, assisted by hypoxic changes in the glycosylation status of endothelial cells that enhance binding to gal-3. Galectin-3's proangiogenic functions were found to be predominantly dependent on the Notch ligand JAG1. Differential direct binding to JAG1 was shown by surface plasmon resonance assay. Upon binding to Notch ligands, gal-3 preferentially increased JAG1 protein half-life over DLL4 and preferentially activated JAG1/Notch-1 signaling in endothelial cells. JAG1 overexpression in Lewis lung carcinoma cells accelerated tumor growth in vivo, but this effect was prevented in Lgals3-/- mice. Our findings establish gal-3 as a molecular regulator of the JAG1/Notch-1 signaling pathway and have direct implications for the development of strategies aimed at controlling tumor angiogenesis.

Original publication

DOI

10.18632/oncotarget.17718

Type

Journal article

Journal

Oncotarget

Publication Date

25/07/2017

Volume

8

Pages

49484 - 49501

Keywords

Jagged-1, Notch, angiogenesis, cancer, galectin-3, Animals, Blood Proteins, Disease Models, Animal, Endothelial Cells, Galectin 3, Galectins, Humans, Hypoxia, Intracellular Signaling Peptides and Proteins, Jagged-1 Protein, Ligands, Membrane Proteins, Mice, Mice, Knockout, Models, Biological, Neoplasms, Neovascularization, Pathologic, Protein Binding, Receptors, Notch, Signal Transduction