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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ben-jacob, Eshel Onuchic, José N. Boareto, Marcelo Jolly, Mohit Kumar |
| Description | Author Affiliation: Boareto M ( Center for Theoretical Biological Physics, Rice University, Houston, TX 77005); Jolly MK ( Center for Theoretical Biological Physics, Rice University, Houston, TX 77005); Ben-Jacob E ( Center for Theoretical Biological Physics, Rice University, Houston, TX 77005); Onuchic JN ( Center for Theoretical Biological Physics, Rice University, Houston, TX 77005); |
| Abstract | Angiogenesis is critical during development, wound repair, and cancer progression. During angiogenesis, some endothelial cells adopt a tip phenotype to lead the formation of new branching vessels; the trailing stalk cells proliferate to develop the vessel. Notch and VEGF signaling mediate the selection of these tip endothelial cells. However, how Jagged, a Notch ligand that is overexpressed in cancer, affects angiogenesis remains elusive. Here, by developing a theoretical framework for Notch-Delta-Jagged-VEGF signaling, we found that higher production levels of Jagged destabilizes the tip and stalk cell fates and can give rise to a hybrid tip/stalk phenotype that leads to poorly perfused and chaotic angiogenesis, which is a hallmark of cancer. Consistently, the signaling interactions that restrict Notch-Jagged signaling, such as Fringe, cis-inhibition, and increased production of Delta, stabilize tip and stalk fates and limit the existence of hybrid tip/stalk phenotype. Our results underline how overexpression of Jagged can transform physiological angiogenesis into pathological one. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 29 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Calcium-Binding Proteins Metabolism Cell Lineage Intercellular Signaling Peptides And Proteins Membrane Proteins Neoplasms Blood Supply Pathology Neovascularization, Pathologic Neovascularization, Physiologic Drug Effects Ligands Models, Biological Receptors, Notch Signal Transduction Vascular Endothelial Growth Factor A Pharmacology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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