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

Decorin is a devouring proteoglycan: Remodeling of intracellular catabolism via autophagy and mitophagy.
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DOI:
10.1016/j.matbio.2017.10.005
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发表时间:
2019-01
期刊:
Matrix biology : journal of the International Society for Matrix Biology
影响因子:
--
通讯作者:
Iozzo RV
Iozzo RV
中科院分区:
其他
文献类型:
--
作者:
Buraschi S;Neill T;Iozzo RV

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自噬是一种基本的、进化保守的真核生物途径,它协调了一种复杂的平衡行为,以实现适当的细胞功能和体内平衡的营养和能量需求。我们发现可溶性蛋白聚糖通过直接与受体酪氨酸激酶(包括VEGF受体2和Met)相互作用,在内皮细胞和乳腺癌细胞中引起自噬和线粒体自噬。在这种情况下,自噬调节被认为是“非规范的”,并由富含亮氨酸的小蛋白聚糖,decorin的生物活性集中体现。可溶性基质来源的信号在受体接合的下游被转导,聚集在一个新发现的自噬机制的联系上,包括内皮细胞自噬的Peg3和肿瘤细胞自噬的有丝分裂抑制素。在这篇专题综述中,我们将概述decorin介导的自噬和有丝自噬,并提出调节细胞内分解代谢是decorin作为一种有效的肿瘤抑制剂的多功能性的潜在分子基础。
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.
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