By Anurag Paul, Neurobiology
Advisor: Maria Czyzyk-Krzeska
Abstract: Autophagy is a homeostatic process that has both tumor-promoting and tumor-suppressing activities. It supports tumor growth by generating nutrients for survival under deprived conditions. Autophagy is induced by serum starvation of cells. Microtubule-Associated Protein 1 Light Chains (MAP1 LC3s) are proteins found in the membranes of autophagosomes and are autophagic regulators. LC3A, LC3B, and LC3C are paralogous genes. LC3B and LC3C-dependent autophagy are important in the oncogenic process during the development of clear cell renal cell carcinoma (ccRCC), the most common and malignant type of kidney cancer. The mechanism of LC3C tumor-suppressing autophagy is not well understood. Therefore, to gain an understanding of the mechanisms of LC3C tumor-suppressing autophagy, we investigated the biological conditions and mechanisms of how the expression of LC3C is regulated, specifically how induction of mRNA expression is regulated by serum starvation and how that differs between LC3B and LC3C. Two different human cell lines, CAKI-1 & 786-0 WT, derived from clear cell renal cell carcinoma tumors that express wild VHL were serum-starved for different lengths of time (6H, 12H, 24H, 30H, 36H, 48H) in media containing 0.1% fetal bovine serum (FBS). Control cells were grown in 10% FBS. In both 786-0 WT and CAKI-1 cell lines, serum starvation resulted in a long-lasting, much stronger induction of mRNA expression of LC3C as compared to LC3B. This signifies an important role of the LC3C paralog in regulating autophagy in human cells, which has potential implications for the cellular metabolism of ccRCC tumors.