Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 49, Pages 16797-16812Publisher
ELSEVIER
DOI: 10.1074/jbc.REV120.014391
Keywords
AMP-activated kinase (AMPK); cell signaling; proteoglycan; perlecan; decorin; extracellular matrix; autophagy; angiogenesis; hyaluronan; endothelial cell; hyaluronan synthase 2; vascular biology
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Funding
- National Institutes of Health [RO1 CA39481, CA47282, CA245311, T32 AR052273]
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The extracellular matrix encompasses a reservoir of bioactive macromolecules that modulates a cornucopia of biological functions. A prominent body of work posits matrix constituents as master regulators of autophagy and angiogenesis and provides molecular insight into how these two processes are coordinated. Here, we review current understanding of the molecular mechanisms underlying hyaluronan and HAS2 regulation and the role of soluble proteoglycan in affecting autophagy and angiogenesis. Specifically, we assess the role of proteoglycan-evoked autophagy in regulating angiogenesis via the HAS2-hyaluronan axis and ATG9A, a novel HAS2 binding partner. We discuss extracellular hyaluronan biology and the post-transcriptional and post-translational modifications that regulate its main synthesizer, HAS2. We highlight the emerging group of proteoglycans that utilize outside-in signaling to modulate autophagy and angiogenesis in cancer microenvironments and thoroughly review the most up-to-date understanding of endorepellin signaling in vascular endothelia, providing insight into the temporal complexities involved.
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