Decorin Evokes a Pro-lysosomal Pathway in Lymphatic Endothelial Cells.
Gabriel J Pascal, Dipon K Mondal, Sadie Kim, Christopher Xie, Devanarayanan Siva Sankar, Jörn Dengjel, Renato V Iozzo
Abstract
Open AccessThe lymphatic system is critical to the body's immune and circulatory system, and lymphangiogenesis, the development of new lymphatic vessels from pre-existing ones is a significant process capitalized upon by cancer during tumorigenesis. Decorin is a small leucine-rich proteoglycan which we have previously shown to be anti-tumorigenic and a suppressor of lymphangiogenesis. We have also shown that decorin exercises its anticancer properties through its ability to evoke autophagy. Through a comprehensive and unbiased proteomic analysis, we explored the implications of decorin exposure on protein expression within mouse lymphatic endothelial cells. We discovered that decorin enriches several protein pathways, notably proteasomal degradation and lysosomal pathways. Several proteins within these pathways such as lysosome associated membrane protein 1 (Lamp1) and Neural precursor cell expressed developmentally downregulated protein 8 (Nedd8) were differentially regulated following decorin treatment. These proteins and their functional pathways should be considered therapeutic targets and emerge as candidates for further exploration within the context of decorin and cancer suppression.