Northern Illinois University
Department of Biological Sciences
College of Liberal Arts and Sciences

Professor Barrie P. Bode, Chair

My laboratory studies the role and regulation of amino acid transporters in human cancer cell growth and survival signaling. Specifically, we focus on two amino acid transporters: ASCT2 (encoded by the SLC1A5 gene) and LAT1 (encoded by the SLC7A5 gene). A bioinformatics study from our laboratory showed that expression of both transporters is coordinately enhanced in a broad spectrum of human cancers compared to corresponding normal tissue. In normal liver, expression of ASCT2 and LAT1 is nearly undetectable, but is robustly increased upon cancerous transformation, making these transporters potential targets for directed therapies in hepatocellular carcinoma (HCC) – a cancer with limited treatment options, a poor prognosis and high mortality rates. Both ASCT2 and LAT1 are amino acid exchangers and have been shown to physically associate in a plasma membrane-localized complex with monocarboxylic acid (e.g. lactate and pyruvate) transporters (MCT) in human cancer cells. This collection of transporters (ASCT2, LAT1, MCT1/2) and associated chaperone proteins (CD98, CD147) has been termed the Metabolic Activation - related Complex ((MArC); Xu and Hemler, Mol Cell Proteomics 4:1061-1071, 2005). Work from our laboratory demonstrated an essential role for ASCT2 expression in human liver cancer growth and survival, as its targeted silencing led to rapid growth cessation and programmed cell death, independent of its role in amino acid delivery. Thus, nutrient transporters not only deliver nutrients, but also appear to play other roles in cellular signal transduction by mechanisms that are currently unknown.