In Australia, cancer results in more than 48,000 deaths each year, a number that is projected to rise in the coming years despite the advances in early diagnosis and treatment. Recent evidence suggests that autophagy may constitute a promising therapeutic target in numerous cancers due to its ability to provide essential nutrients to the cancer cell and to increase cancer cell survival, and its role in the acquired resistance to current therapeutics. Autophagy helps to maintain the balance of cellular energy and nutrients through the degradation of damaged organelles and proteins via the lysosome. The lysosomal associated membrane protein 2 (LAMP-2) is found on the lysosome and is heavily involved in autophagy. LAMP-2 has three isoforms LAMP-2A, LAMP-2B and LAMP-2C. Previous research has established the role of LAMP-2A in chaperone-mediated autophagy, but the role of LAMP-2B and LAMP-2C is more unclear, especially in the context of cancer.
The expression levels of the LAMP-2 isoforms LAMP-2A and LAMP-2B were explored in a panel of breast cancer cell lines with different metastatic propensities. The expression levels of the two isoforms were comparatively different from each other but did not correlate with the metastatic potential of the cell lines studies. We next explored the effect of stressors on LAMP-2A and LAMP-2B in breast cancer cell lines and found that the isoforms responded distinctly to different stressors. Autophagy is known to increase in response to stress, however, the differences between these isoforms in response to stress has yet to be fully explored. Autophagy has been implicated in the increased aggressiveness of cancer, thus the function and the differences of the LAMP-2 isoforms warrants further investigation. The findings from this study will provide an essential delineation of the role of these autophagy related isoforms in cancer, determining whether they promote or inhibit the metastatic phenotype, thereby identifying new therapeutic targets.