The Role of Decorin and Biglycan Signaling in Tumorigenesis

Abstract

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer development. In this review, we summarize growing evidence for the complex roles of decorin and biglycan signaling in tumor biology and address potential novel therapeutic implications.

Simple gene signature to assess murine fibroblast polarization

“…It was therefore important to add other features to assess the profibrotic polarization, such as matrix crosslinking, matrix degradation, and matrix microenvironment. Matrix crosslinking regulate matrix stiffness 26 – 28 . Lysyl oxidases (LOXs) and lysyl oxidase‐like 1‐4 (LOXL 1‐4) are a group of enzymes that catalyzes cross-linking of collagens, thereby rendering these matrix proteins unable to be degraded.…”

“…The ECM is a very complex three-dimensional structure that is not only limited to a mechanical support role but whose elements are also involved in various signaling pathways and cellular processes, including inflammation, proliferation, apoptosis, and angiogenesis. Among these elements, proteoglycans critically provide structure to the ECM, but also regulate many signaling pathways, such as growth factors, cytokines, chemokines, and matrix-cell contacts 6 , 26 , 34 . Decorin is a crucial proteoglycan, also called “the guardian from the matrix”, that “decorates” collagen fibrils and regulates the cell cycle by trapping TGFß 34 , 35 .…”

“…Decorin is a crucial proteoglycan, also called “the guardian from the matrix”, that “decorates” collagen fibrils and regulates the cell cycle by trapping TGFß 34 , 35 . Decorin has also the ability to act as a pan-receptor inhibitor of tyrosin kinases, including epidermal growth factor receptor, vascular endothelial growth factor receptor 2, mesenchymal-epithelial transition factor receptor; thus restraining angiogenesis 26 , 36 . The selection of decorin brings new insights in the assessment of fibroblast polarization.…”

The Role of Decorin in Autoimmune and Inflammatory Diseases

“…As an endogenous antagonist of transforming growth factor β (TGF- β ), decorin can physically interact with TGF- β , interfere with TGF- β signaling, and form decorin/TGF- β complexes in the extracellular matrix, thereby significantly attenuating the profibrotic effect of TGF- β [ 21 ]. In tumors, decorin has been shown to inhibit metastasis, tumor cell proliferation, and angiogenesis and regulate autophagy and inflammation [ 22 ]. In addition to these characteristics, decorin, as one of the damage-associated molecular patterns (DAMPs), can initiate aseptic inflammation and induce the activation of innate immune cells, which provides the basis for its involvement in autoimmune and inflammatory diseases [ 11 , 23 ].…”

“…Decorin is the first extracellular matrix component identified to influence cellular metabolic processes. The role of decorin in mitochondrial autophagy in epithelial-derived tumors and endothelial cells has been widely reported [ 22 ]. Decorin induced the expression of mitostatin in breast cancer, leading to mitochondrial ultrastructural changes [ 63 , 64 ].…”