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Journal article
Endorepellin-evoked Autophagy Contributes to Angiostasis
The Journal of biological chemistry, v 291(37), pp 19245-19256
09 Sep 2016
PMID: 27435676
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Endorepellin, the C-terminal domain of perlecan, is an angiostatic molecule that acts as a potent inducer of autophagy via its interaction with VEGFR2. In this study, we examined the effect of endorepellin on endothelial cells using atomic force microscopy. Soluble endorepellin caused morphological and biophysical changes such as an increase in cell surface roughness and cell height. Surprisingly, these changes were not accompanied by alterations in the endothelial cell elastic modulus. We discovered that endorepellin-induced autophagic flux led to co-localization of mammalian target of rapamycin with LC3-positive autophagosomes. Endorepellin functioned upstream of AMP-activated kinase α, as compound C, an inhibitor of AMP-activated kinase α, abrogated endorepellin-mediated activation and co-localization of Beclin 1 and LC3, thereby reducing autophagic progression. Functionally, we discovered that both endorepellin and Torin 1, a canonical autophagic inducer, blunted ex vivo angiogenesis. We conclude that autophagy is a novel mechanism by which endorepellin promotes angiostasis independent of nutrient deprivation.
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Details
- Title
- Endorepellin-evoked Autophagy Contributes to Angiostasis
- Creators
- Atul Goyal - Kimmel Cancer CenterMaria A. Gubbiotti - Kimmel Cancer CenterDaphney R. Chery - Drexel UniversityLin Han - Drexel UniversityRenato V. Iozzo - Kimmel Cancer Center
- Publication Details
- The Journal of biological chemistry, v 291(37), pp 19245-19256
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000383242800004
- Scopus ID
- 2-s2.0-84987650441
- Other Identifier
- 991019168724604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology