Oncosuppressive functions of decorin.
The extracellular matrix is rapidly emerging as a prominent contributor to various fundamental processes of tumorigenesis. In particular, decorin, a member of the small leucine-rich proteoglycan gene family, is assuming a central role as a potent soluble tumor repressor. Decorin binds and antagonizes various receptor tyrosine kinases and inhibits downstream oncogenic signaling in several solid tumors. Among other functions, decorin evokes cell cycle arrest, apoptosis, and antimetastatic, and antiangiogenic programs. Recent work has revealed a paradigmatic shift in our understanding of the molecular mechanisms underlying its tumoricidal properties. Decorin adversely compromises the genetic signature of the tumor microenvironment and induces endothelial cell autophagy downstream of VEGFR2. Moreover, decorin selectively evokes destruction of tumor cell mitochondria downstream of Met through mitophagy. Acting as a partial agonist, decorin signals via proautophagic receptors and triggers procatabolic processes that parallel the classical tumoricidal properties of this multifaceted proteoglycan.
Department of Pathology; Anatomy and Cell Biology; and the Cancer Cell Biology and Signaling Program; Kimmel Cancer Center ; Thomas Jefferson University ; Philadelphia, PA USA.
Thomas
T
Neill
Department of Pharmacology; Goethe University ; Frankfurt, Germany.
Liliana
L
Schaefer
Department of Pathology; Anatomy and Cell Biology; and the Cancer Cell Biology and Signaling Program; Kimmel Cancer Center ; Thomas Jefferson University ; Philadelphia, PA USA.
Renato V
RV
Iozzo
Peg3; angiostasis; autophagy; mitophagy; mitostatin; proteoglycans