Abstract by Monique Speirs
Chemistry and Biochemistry
A kinetic proteomics approach to identify targets of autophagy in colorectal cancer and increase treatment specificity
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Chemoresistance severely limits treatment options and increases the risk of CRC recurrence. Autophagy is a conserved protein degradation system that plays a pro-survival role in CRC cells under microenvironmental stress. Recent literature indicates that nonspecific anti-autophagy drugs like chloroquine (CQ) sensitize CRC cells to chemotherapy. Yet, the exact role and mechanisms of autophagy in CRC are unknown. We used quantitative and kinetic proteomics techniques to measure the global effects of CQ on the proteome and identify cellular structures targeted by autophagy in CRC cell culture and animal models. While CQ reduced global protein turnover, specific protein classes were significantly sensitive to CQ-induced autophagy inhibition in CRC cells. We have shown that the autophagy substrate selection process is measurable and may be used as a means to identify highly specific anti-autophagy drug targets in CRC and circumvent chemoresistance mechanisms.