Project 466733

Autophagy is a conserved cellular degradation pathway that regulates cell survival and invasion. There is a dual role of autophagy in tumour suppression and progression depending on the cancer. This dynamic role is of clinical importance as autophagy inhibitors are being developed in clinical trials and clinicians must determine which patients would benefit from this treatment. Autophagy protein LC3C selectively binds and targets the Met receptor for degradation. Met signaling is linked to poor prognoses in some cancers and can trigger cell invasion when activated. Our lab has shown LC3C negatively regulates Met and is down-regulated in various cancers, including breast cancer (BRCA), suggesting an anti-tumorigenic role. My research objective is to determine LC3Cs role in BRCA development and how it inhibits tumour progression, which I hypothesize is by inhibiting cell invasion. I will test this in the following aims: 1. Characterizing the role of LC3C in BRCA and tumour progression. In BRCA patient-derived tissues and mouse models, I will study how LC3C expression affects metastasis and how activating Met signaling impacts cell invasion. 2. Determining how LC3C inhibits cell invasion. Using a proximity-based interaction screen of LC3C, I will choose top novel interaction candidates linked to cell migration using protein interaction prediction tools. I will characterize the cellular mechanism by which LC3C regulates invasion and these proteins in cells. This project will deduce the novel role of LC3C in cancer, regulating cell invasion, and confirm LC3C is a component of an anti-tumorigenic autophagy pathway in BRCA. The knowledge gained from my research will be applicable clinically when determining if autophagy inhibitors are the correct line of treatment.