What is Autophagy?
Autophagy is a well-conserved survival mechanism that plays a cellular house keeping function in promoting the regular degradation of protein aggregates, organelles, pathogens and other large intra-cellular structures by autolysosomes -“garbage disposal” – and thus plays a key role in maintaining cellular integrity and promoting efficient cellular function.
Autophagy is also ramped up in response to energy deficits (such as in an ischemic tumor) when it becomes critical for generating ATP and metabolites for survival. Thus, not only is autophagy the “garbage collector” – autophagy also promotes “re-cycling”.
Why is Autophagy important in cancer?
Autophagy plays a complex role in cancer development and treatment that currently appears to vary depending on tissue type, driving oncogene, stage of tumor progression and drug regimen used.
This highlights the need to understand which aspects of autophagy are most critical to its role in cancer if we are to effectively target autophagy for improved cancer therapy.
The diverse functions of autophagy in the cell include promoting amino acid recycling at the lysosome, eliminating unfolded protein and reducing ER stress, turning over mitochondria, recruiting immune cells to tumors and in regulating secretion of cytokines and proteases to break down the basement, and as our recent data shows, promoting focal adhesion dis-assembly to allow tumor cell invasion and metastasis.
Our work has focused on two key consequences of altered autophagy in cancer: (1) dysfunctional mitochondria arising from defects in mitophagy (the process by which mitochondria are selectively degraded at the autophagolysosome), and (2) increased metastasis due to a variety of roles for autophagy in tumor cell invasivion.