Abstract 2836: Effect of autophagy inhibition on epithelial mesenchymal transition in breast cancer cell lines

Abstract

Abstract The aim of our work is to evaluate potential undesirable effects of autophagy inhibition in breast cancer subtypes which are not sensitive to the inhibition of autophagy. Worldwide, BC is the most frequent cancer in women. Despite recent advances in diagnosis, molecular stratification and targeted therapy, BC is still the leading cause of cancer-related death in women. Thus, it is a public health issue that must be attended. In cancer, autophagy has a pro-tumorigenic role that helps tumor cells survive metabolic stress and growth factor deprivation, hypoxia, maintain tumor initiating cells, confer therapy resistance and modulate epithelial mesenchymal transition (EMT). Because tumor cells benefit from autophagy, it has been proposed that autophagy inhibition could be beneficial for cancer treatment. Nowadays, there are clinical trials where autophagy is being inhibited with promising results that encourage this approach. However, in these clinical trials, cancer types are not been stratified and autophagy is being inhibited in many solid tumor types. In this regard, there is also in vitro evidence in which autophagy inhibition in some cancer types induces EMT, which in the clinic could be detrimental for patients. This highlights the urgency for stratifying patients that will benefit the most from autophagy inhibition. In this work, autophagy inhibition in MCF7 ER+ cell line increased secretion, inflammation and EMT related pathways suggesting induction of malignancy. Autophagy inhibition induced changes in cell morphology in ER+ breast cancer cell lines (MCF7 and T47D) when evaluated by aspect ratio estimation changing from a cobblestone -like epithelial morphology to a fibroblast-like morphology. No changes in cell morphology were found in MCF10A and MDAMB231 cell lines. Changes in morphology were accompanied by a decrease in E-cadherin protein levels suggesting induction of EMT. Our results suggest that CQ treatment in ER+ BC cells could induce a malignant process related to EMT. Thus, ER+ BC patients may not benefit from autophagy inhibition. Nowadays, there are clinical trials where autophagy is being inhibited and no subtype stratification is being done, so we encourage to stratify patients to determine who will be benefited the most from autophagy inhibition and who will not. Citation Format: Guadalupe Rojas, Nidia Pazos, Paola Maycotte. Effect of autophagy inhibition on epithelial mesenchymal transition in breast cancer cell lines [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 2836.