Catabolic degradation of endothelial VEGFA via autophagy
Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo
Abstract
Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.
Topics & Concepts
AutophagyDegradation (telecommunications)CatabolismCell biologyVascular endothelial growth factor AChemistryVEGF receptorsBiologyBiochemistryCancer researchComputer scienceVascular endothelial growth factorMetabolismApoptosisTelecommunicationsAutophagy in Disease and TherapyAdvanced Glycation End Products researchLipid metabolism and biosynthesis