Abstract PO2-28-03: E-Cigarette Aerosol Exposure: Unraveling the Nexus of Autophagy, Cancer Stem Cells, and EMT in Breast Cancer Metastasis

Abstract Electronic cigarettes (E-cigs) have emerged as a significant public health concern due to their increasing popularity. These products have been associated with various harmful effects on human health. In the United States, breast cancer is the most diagnosed cancer among women, and its recurrence and metastasis are primary contributors to morbidity and mortality. Two critical factors in cancer progression are Epithelial-mesenchymal transition (EMT) and Cancer stem-like cells (CSCs), both of which play pivotal roles in metastasis. As a result, targeting the signaling pathways involved in these processes has become a promising avenue for cancer therapy. Autophagy, a cellular process, has dual roles in cancer development depending on the cancer type and stage. Given these considerations, our hypothesis centers on disrupting the EMT-mediated metastatic cascade in breast cancer by targeting autophagy in Cancer Stem Cells (CSCs). To investigate this hypothesis, we conducted experiments using mouse breast epithelial cells (HC11) and Triple-negative mouse breast cancer cells (4T1) exposed to E-cig aerosol at the air-liquid interphase (ALI) for 1 hr followed by a 24 hr recovery period. Our findings indicate that exposure to E-cig aerosols led to a decrease in epithelial markers (E-Cadherin and β-catenin) and an increase in mesenchymal markers (N-Cadherin and Vimentin) in HC11 cells. This suggests that normal cells may acquire characteristics associated with solitary migration. Furthermore, we observed significant changes in the levels of autophagy-related proteins (LC3B, Beclin-1, ATG12, and ATG16) and upregulation of stem cell markers (OCT4, SOX2, NANOG, KLF4, and c-MYC) in response to E-cig aerosol exposure, both in HC11 and 4T1 cells. Additionally, these alterations extended to changes in the expression of genes associated with the Transforming Growth Factor-beta (TGF-β) signaling pathway, known to play a potential role in promoting EMT. Our results provide a deeper understanding of the interplay between EMT, CSCs, and the autophagy process in the context of ALI exposure in normal and cancer cells. This underscores the need for further research into the shared molecular mechanisms of these three processes to identify common therapeutic targets that can simultaneously affect them. Citation Format: Shilpa Thota, Rizwana Begum, Naveen Chintalaramulu, Biplov Sapkota, Abhishek Pandit. E-Cigarette Aerosol Exposure: Unraveling the Nexus of Autophagy, Cancer Stem Cells, and EMT in Breast Cancer Metastasis abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-03.