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2015 ; 2
(3
): e975645
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Oncosuppressive functions of decorin
#MMPMID27308453
Neill T
; Schaefer L
; Iozzo RV
Mol Cell Oncol
2015[Jul]; 2
(3
): e975645
PMID27308453
show ga
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.
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