Autophagy, cancer and angiogenesis: where is the link?

Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions.

While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells.

Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.