Decorin is a devouring proteoglycan: Remodeling of intracellular catabolism via autophagy and mitophagy

Matrix Biol. 2019 Jan;75-76:260-270. doi: 10.1016/j.matbio.2017.10.005. Epub 2017 Nov 7.

Abstract

Autophagy, a fundamental and evolutionarily-conserved eukaryotic pathway, coordinates a complex balancing act for achieving both nutrient and energetic requirements for proper cellular function and homeostasis. We have discovered that soluble proteoglycans evoke autophagy in endothelial cells and mitophagy in breast carcinoma cells by directly interacting with receptor tyrosine kinases, including VEGF receptor 2 and Met. Under these circumstances, autophagic regulation is considered "non-canonical" and is epitomized by the bioactivity of the small leucine-rich proteoglycan, decorin. Soluble matrix-derived cues being transduced downstream of receptor engagement converge upon a newly-discovered nexus of autophagic machinery consisting of Peg3 for endothelial cell autophagy and mitostatin for tumor cell mitophagy. In this thematic mini-review, we will provide an overview of decorin-mediated autophagy and mitophagy and propose that regulating intracellular catabolism is the underlying molecular basis for the versatility of decorin as a potent oncosuppressive agent.

Keywords: Met; Mitostatin; Peg3; Receptor tyrosine kinases; Small leucine rich proteoglycans; VEGFR2.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Autophagy / genetics*
  • Decorin / genetics*
  • Humans
  • Kruppel-Like Transcription Factors / genetics*
  • Metabolism / genetics
  • Mitophagy / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Signal Transduction / genetics
  • Tumor Suppressor Proteins / genetics*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

  • DCN protein, human
  • Decorin
  • Kruppel-Like Transcription Factors
  • PEG3 protein, human
  • Tumor Suppressor Proteins
  • mitostatin protein, human
  • KDR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Vascular Endothelial Growth Factor Receptor-2