The importance of proteoglycans as regulators of key cellular processes such as angiogenesis, adhesion, and inflammation has long been appreciated. However, a new era appears to be dawning for the role of proteoglycans in the regulation of autophagy, a homeostatic mechanism whereby organelles and other cytoplasmic contents are degraded and recycled via lysosomal processing [1]. Depending on the context, autophagy has been regarded as either a cell-survival or cell-death pathway. For example, following starvation, a cell will undergo autophagy in order to break down cellular components for re-utilization, allowing the cell to survive under nutrient-poor conditions [2]. In contrast, when programmed cell death pathways are impaired, autophagy may substitute for apoptosis leading to cell death [3,4]. While basal autophagy is required for normal cell maintenance and contributes to standard cell signaling, aberrant autophagy has been implicated in a range of disease processes including diabetes, inflammation, and neurodegenerative disorders [–8]. In the setting of cancer, the function of autophagy has been difficult to discern. Where some studies indicate that autophagy is beneficial for tumor cell survival [9,10], others suggest that the self-degradative process may prevent tumor growth during early stages of tumorigenesis by shielding healthy cells from damage due to protein aggregation and build-up of other by-products of metabolic turnover [5,11]. The complexity of this pathway lends itself to scrutiny in order to gain a better understanding of its regulation as well as its overall function in normal cell signaling and disease. Recent studies illustrate that select proteoglycans and other matrix constituents dynamically contribute to autophagic regulation [–19]. In this commentary we will consider the noteworthy role of the following three matrix components in the regulation of the autophagic process: 1) The small leucine-rich proteoglycan, decorin, 2) The basement membrane heparan sulfate proteoglycan, perlecan, and 3) The C-terminal fragment of perlecan, endorepellin.
Keywords: AMPK; Beclin 1; Decorin; Endorepellin; LC3; Peg3; Perlecan.