The Role of Decorin Proteoglycan in Mitophagy

被引:10
作者
Neill, Thomas [1 ]
Iozzo, Renato V. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA
基金
美国国家卫生研究院;
关键词
small leucine-rich proteoglycans; autophagy; Peg3; VEGFR2; MET; mitostatin; GROWTH-FACTOR-BETA; LEUCINE-RICH PROTEOGLYCANS; BREAST-CARCINOMA CELLS; IMPRINTED GENE PEG3; MECHANICAL-PROPERTIES; TUMOR-SUPPRESSOR; HEPARAN-SULFATE; ENDOPLASMIC-RETICULUM; EXTRACELLULAR-MATRIX; CELLULAR CLEARANCE;
D O I
10.3390/cancers14030804
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary The eminent rise of extracellular matrix constituents, chiefly hailing from the proteoglycan gene family, has revolutionized our understanding of how intracellular catabolism is regulated at the intersection of autophagy and breast cancer. In this review, we examine the mechanisms of decorin, a small leucine-rich proteoglycan, as it relates to autophagy and mitochondrial autophagy (mitophagy). In each case, decorin signals via a unique cell surface receptor tyrosine kinase to evoke autophagy (VEGFR2) or mitophagy (MET receptor) that converges on a novel tumor suppressor gene. The downstream function of either Peg3 or mitostatin in response to decorin manifests as potent means to subdue breast cancer development and progression. Proteoglycans are emerging as critical regulators of intracellular catabolism. This rise in prominence has transformed our basic understanding and alerted us to the existence of non-canonical pathways, independent of nutrient deprivation, that potently control the autophagy downstream of a cell surface receptor. As a member of the small leucine-rich proteoglycan gene family, decorin has single-handedly pioneered the connection between extracellular matrix signaling and autophagy regulation. Soluble decorin evokes protracted endothelial cell autophagy via Peg3 and breast carcinoma cell mitophagy via mitostatin by interacting with VEGFR2 or the MET receptor tyrosine kinase, respectively. In this paper, we give a mechanistic perspective of the vital factors underlying the nutrient-independent, SLRP-dependent programs utilized for autophagic and/or mitophagic progression in breast cancer. Future protein therapies based on decorin (or fellow proteoglycan members) will represent a quantum leap forward in transforming autophagic progression into a powerful tool to control intracellular cell catabolism from the outside.
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页数:19
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