The tumor microenvironment plays a determining role in cancer development through a plethora of interactions between the extracellular matrix and tumor cells. Decorin is a prototype member of the SLRP family found in a variety of tissues and is expressed in the stroma of various forms of cancer. Decorin has gained recognition for its essential roles in inflammation, fibrotic disorders, and cancer, and due to its antitumor properties, it has been proposed to act as a "guardian from the matrix." Initially identified as a natural inhibitor of transforming growth factor-β, soluble decorin is emerging as a pan-RTK inhibitor targeting a multitude of RTKs, including EGFR, Met, IGF-IR, VEGFR2, and PDGFR. Besides initiating signaling, decorin/RTK interaction can induce caveosomal internalization and receptor degradation. Decorin also triggers cell cycle arrest and apoptosis and evokes antimetastatic and antiangiogenic processes. In addition, as a novel regulatory mechanism, decorin was shown to induce conserved catabolic processes, such as endothelial cell autophagy and tumor cell mitophagy. Therefore, decorin is a promising candidate for combatting cancer, especially the cancer types heavily dependent on RTK signaling.
Keywords: Angiogenesis; Autophagy; Cell cycle; Decorin; EGFR; Extracellular matrix; Growth factor; Inflammation; Met; Mitophagy; Receptor tyrosine kinase; SLRP; Signaling; Stroma; Tumor.