Autophagy is a highly conserved catabolic process resulting in the degradation of organelles and proteins into recyclable nutrients in response to cellular stress to maintain homeostasis. However, its role in the context of cancer has been somewhat paradoxical in that it has been shown to prevent tumorigenesis via protein aggregate degradation yet paradoxically it can also facilitate the survival and maintenance of the metastatic phenotype. The role of autophagy and the mechanisms that underlie its activity, within the varying contexts of cancer, are still not well understood and require elucidation.
We have examined a breast cancer cell line panel for key autophagy markers which were found to be increased in expression in breast cancer subtypes with a more aggressive phenotype. This increase was supported by functional studies of autophagic activity, where a high autophagic flux was observed at basal conditions. Interestingly, activation of autophagy above baseline resulted in a dysregulation of its activity, indicating that the basal level of autophagic activity in aggressive breast cancer cells had reached maximal autophagic capacity. The requirement for autophagy in these cells was confirmed by treatment of the cell lines with specific autophagic inhibitors resulting in cell death. No cell death was observed in the immortalised breast epithelial cell line, MCF10A. A key modulator of autophagy, MAP1LC3, was investigated in regards to isoform expression in patient data, significantly, expression of two of the isoforms associated with increased overall patient survival while one correlated with decreased patient survival. Consistent with this, in vitro investigation of the MAP1LC3 isoforms in the breast cancer panel demonstrated isoform expression at basal conditions and in response to stress that could delineate the aggressive phenotype of the cell line. We propose that variations in MAP1LC3 isoform expression may lend themselves as future biomarkers for targeted autophagic therapeutics.