Galectin-3 acts as an angiogenic switch to induce tumor angiogenesis via Jagged-1/Notch activation

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...

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Veröffentlicht in:Oncotarget Jg. 8; H. 30; S. 49484
Hauptverfasser: Dos Santos, Sofia Nascimento, Sheldon, Helen, Pereira, Jonathas Xavier, Paluch, Christopher, Bridges, Esther M, El-Cheikh, Márcia Curry, Harris, Adrian L, Bernardes, Emerson Soares
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 25.07.2017
Schlagworte:
Animals
Blood Proteins
Disease Models, Animal
Endothelial Cells - metabolism
Galectin 3 - genetics
Galectin 3 - metabolism
Galectins
Humans
Hypoxia - metabolism
Intracellular Signaling Peptides and Proteins - metabolism
Jagged-1 Protein - metabolism
Ligands
Membrane Proteins - metabolism
Mice
Mice, Knockout
Models, Biological
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Protein Binding
Receptors, Notch - metabolism
Signal Transduction
cancer
Jagged-1
galectin-3
angiogenesis
Notch
ISSN:1949-2553, 1949-2553
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Zusammenfassung: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.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.17718