Abstract 1160: Endoplasmic reticulum stress disrupts stemness-related transcriptional regulatory network: Implication for therapy response in cancer

Abstract Pancreatic cancer is the third leading cause of cancer-associated deaths in the United States. We have recently demonstrated that endoplasmic reticulum (ER) stress correlates with improved survival in human pancreatic cancer patients on gemcitabine therapy. Cancer cell stemness is a significant contributor of poor response to therapy and disease recurrence. We also observed that inducing ER stress can diminish stemness in cancer cells. Hence, to investigate the mechanism of ER stress-mediated alterations in diminishing cancer stemness, we investigated the impact of ER stress on transcriptomic alterations by performing RNAseq studies. We subjected cancer cells to treatment with thapsigargin and the harvested mRNA was utilized for RNAseq analysis. We observed significant alterations in mRNA expression levels of the stemness-associated gene set, which also showed significant enrichment in Ingenuity pathway analysis. Hence, our studies demonstrate that ER stress regulates stemness at the transcriptional level. Our ongoing and future studies will target individual genes/pathways to identify their relative contributions to ER stress-mediated regulation of stemness. Considering the role of stemness in disease recurrence, our studies will provide novel mechanistic insights that may lead to novel therapies for targeting disease recurrence in pancreatic cancer. Citation Format: Appolinaire Olou, Kamiya Mehla, Pankaj Singh. Endoplasmic reticulum stress disrupts stemness-related transcriptional regulatory network: Implication for therapy response in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1160.