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Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage
Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage
Dissertations & Theses (Open Access)
Neuroblastoma is the most common malignancy in infants. Overexpression of the epidermal growth factor receptor (EGFR) in neuroblastoma tumors can result in enhanced EGFR signaling, uncontrolled proliferation, and may provide a mechanism for chemotherapy resistance. UBE4B, an E3/E4 ubiquitin ligase, ubiquitinates the EGFR and promotes its lysosomal degradation ultimately attenuating EGFR signaling. Interestingly, the UBE4B gene lies in a chromosomal region (1p36) whose loss is correlated with poor patient outcomes due to inefficient EGFR degradation and enhanced cell proliferation. We examined whether depletion of UBE4B in a chemoresistant neuroblastoma cell line would affect tumor responses to drugs that specifically target …