ABCG2-mediated cellular adaptation to tobacco smoke exposure
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Krittika Narasimhan
Exhibition Number 212
Abstract
Cigarette smoke contains various carcinogenic compounds and reactive species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Oxidative stress caused by reactive species overload leads to increase in levels of unfolded ubiquitinated protein aggregates in cells. While in normal cells this decreases viability, cancer cells develop mechanisms to adjust to these harsh environments. ABCG2 is a transmembrane transporter protein, also known as the breast cancer resistance protein (BCRP). It acts as an efflux pump for anti-cancer medications, thus conferring drug resistance in various types of cancer. Our previous studies showed that ABCG2 reduces protein aggregation in cigarette smoke concentrate (CSC)-exposed A549 lung cancer cells. The lung cancer cells were treated with CSC eluted in DMSO and microscopic images were captured in intervals to observe protein aggregation and growth. More lung cancer cell lines from smokers were studied for effect against smoke, and it was found that all exhibited higher CSC tolerance when compared to non-cancerous controls. To explore whether these adaptations extend beyond lung cancer, we are currently studying effects of smoke exposure on various cell. Our primary immunostaining studies revealed localization of ABCG2 in monkey kidney cell (CV-1) nuclei, suggesting function beyond membrane-associated efflux role. Understanding ABCG2 localization in response to cigarette smoke will give deeper insight into the mechanisms of cellular adaptations to smoke and mechanisms behind resistance to anti-cancer therapeutics.
Importance
Cigarette smoke contains harmful toxins that lead to fatal diseases like cancers. It has been found that continuing to smoke during cancer treatment worsens the disease prognosis. Many cancers develop resistance towards chemotherapy drugs through various mechanisms, one of them being an increase in the level of ABCG2, a membrane associated efflux protein also known as the breast cancer resistance protein. Our lab found that on exposure to smoke, ABCG2 levels in lung cancer cells increased, and enhanced their viability. Cancer cells adapt and become resistant to smoke, and this resistance to smoke might involve similar mechanisms as the development of chemotherapy resistance, such as an increase in ABCG2. Understanding these mechanisms will help us exploit it for therapeutic purposes.