EPIGENETIC REGULATION OF CELL STATE TRANSITIONS IN TRIPLE NEGATIVE BREAST CANCER

Abstract

During cancer progression, cells would reversibly transit between different cell states that differ in their competence to contribute to survival. The activation of epithelial-mesenchymal transition (EMT) in cancer cells has often been attributed to enhanced tumorigenic potential and therapeutic resistance. Promoting mesenchymal-epithelial transition (MET), the reverse process of EMT, would hence decrease tumorigenicity and improve therapeutic response. As EMT is a dynamic transitional process, metabolic rewiring and epigenetic reprograming are important for regulating the epithelial-mesenchymal plasticity. In this study, a systematic approach was used to identify regulators of cell state reprogramming. Using small molecule library screens on metabolic targets and epigenetic modifiers, I sought to understand the underpinning mechanisms of metabolic and epigenetic influences on cell state transitions. This allowed the identification of MET inducers that could be used as targeted approach for controlling the tumor progression of basal-like breast cancers, which are frequently linked to an active EMT program.