Determining the role of xCT-induced metabolic dysregulation in malignant transformation
Metabolic dysregulation is a hallmark of cancer. Cells that develop an altered metabolism may be predisposed to develop genomic instability. The metabolism of glutathione plays a key role in protecting the cell against DNA damage by reactive oxygen species (ROS). The cystine glutamate antiporter xCT (SLC7A11) and glutamine transporter SLC1A5 are key players in regulating cellular glutathione pool. The goal of my research is to identify metabolic dysregulation focusing on the role of xCT and SLC1A5 in malignant transformation of human bronchial epithelial cells (HBEC). By use of an in vitro model of genetically modified HBEC cells and loss of function and gain of function approach experiments are underway to study the differences in tumorigenicity of the HBEC clones. Understanding the mechanism of dysregulation of these amino acid transporters in the context of lung tumorigenesis may assist in risk stratification strategies and identify potential therapeutic targets.