Abstract 1940: Autophagy mediates leptin induced migration and erk activation in breast cancer cells

Autophagy is an intracellular recycling process active in eukaryotic cells which involves the formation of an autophagosome that delivers cytoplasmic components to the lysosome for degradation. This process occurs at low rates under basal conditions, but it can be induced by diverse stress conditions such as starvation, hypoxia or metabolic disorders. Autophagic flux can also be enhanced in response to hormones, including leptin. Leptin is considered a pro-tumorigenic protein whose circulating levels have been related to a bad prognosis in obese breast cancer patients. It has been recently demonstrated that leptin can induce autophagy in cancer cell lines from different tissues, suggesting that autophagy could modulate the pro-tumorigenic effects associated with leptin. In this study, the role of autophagy in leptin-induced proliferation, migration, apoptosis and ERK phosphorylation in breast cancer cell lines was evaluated. Methods: MCF7 estrogen receptor positive and MDA-MB-231 triple negative breast cancer cell lines were used. MCF7 and MDA-MB-231 cell lines were stimulated with 400 and 50 ng/ml of leptin, respectively. Autophagy was assessed by LC3-II and p62 protein levels by western blot, and autophagosome formation by fluorescence microscopy. Proliferation and migration were assessed by real-time microscopy in an IncuCyte analyzer; and cell death was evaluated by fluorescence analysis of caspase activity. Changes in ERK phosphorylation were measure by western blot. Results: Leptin increased autophagy in MCF7 cells but not in triple negative MDA-MB-231 cells. In MCF7 cells, autophagy inhibition reduced leptin-induced cell proliferation, changes associated to a mesenchymal morphology, cell migration, and ERK activation. In MDA-MB-231 cells, autophagy inhibition reduced proliferation and increased apoptosis independently of leptin treatment. In both cell lines, leptin-induced migration and ERK phosphorylation were reduced by the inhibition of autophagy. Conclusion: Autophagy was important for increased cancer cell migration induced by leptin and for the maintenance of ERK phosphorylation. Our data suggest a potential use for the inhibition of autophagy in breast cancer associated with obesity. Citation Format: Alin Garcia Miranda, Karen A. Solano Alcala, Jose B. Montes Alvarado, Julio Reyes Leyva, Paola Maycotte, Eduardo Castaneda Saucedo. Autophagy mediates leptin induced migration and erk activation in breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1940.