Date of Award
Jane L. Ko, PhD
Constantine Bitsaktsis, PhD
Angela Klaus, PhD
Heping Zhou, PhD
STAT3, Desferrioxamine, WP1066, phosphorylation, Hypoxia, Neuroblastoma, Cell Culture
Oxygen homeostasis is critical for optimal energy production in eukaryotic organisms. The signal transduction pathways involved with detection and mitigation of hypoxia have been carefully scrutinized in an effort to elucidate how metabolism and survival is maintained. Characterization of these pathways and their involvement in physiological processes such as blood cell production in the bone marrow and microvessel formation in developing embryos provides a model of how these functions are executed. Less well-characterized mechanisms in disease states such as solid tumors still confound researchers whose efforts to find effective treatments are falling short. Cancer cells exploit the activities of fundamental signaling pathways to enhance their survival. Aberrant function of the Janus Activated kinase (JAK) pathway and its protein partner, signal transduction and activator of transcription 3 (STAT3) have been linked to many types of cancer, because they mediate cellular processes such as proliferation, metabolism and survival. Significant contradictions persist regarding how each of these functions are achieved. STAT3 is subject to post-translation modifications on two separate amino acid residues, both of which have been linked to solid tumor proliferation and survival. Using desferrioxamine (DFO), a hypoxic mimetic agent, we examined the reaction of human neuroblastoma cells treated with varying concentrations at different time periods. We found significant differences in the post-translational modifications of STAT3 in the cells that survived treatment using flow cytometry. An inhibitor was also used to more closely identify upstream signaling, and to measure its effect on cell viability. Our preliminary data suggests that alterations in the JAK-STAT3 signaling pathway contributes to cell survival under DFO-induced hypoxic conditions.
Harrison, Veronica, "Analysis of Post-Translational Modifications and Expression of STAT3 under Desferrioxamine Induced Hypoxia in Human Neuroblastoma Cells" (2019). Seton Hall University Dissertations and Theses (ETDs). 2712.