Investigating the therapeutic potential of targeting ABCE1 in neuroblastoma (#117)
Neuroblastomas with amplification of the MYCN oncogene are associated with particularly poor clinical outcome (1). Despite the prognostic significance of MYCN, targeting this gene and its product, the MYCN transcription factor, as a form of treatment for neuroblastoma has proven difficult. MYCN heightens the malignancy of neuroblastoma by regulating many downstream genes; one of which is ABCE1 (2). High expression of ABCE1 is associated with reduced neuroblastoma patient survival (2). Encoded by this gene is the ATP-binding cassette subfamily ‘E’ protein (ABCE1) which is a translation factor that may support the growth and spread of cancer cells by enhancing global protein synthesis or by increasing expression levels of specific oncoproteins (3). The aim of this project is to determine how ABCE1 influences neuroblastoma cell growth, migration and invasion of extracellular matrix. Transient ABCE1 suppression, by siRNA transfection, inhibited colony formation by stimulating apoptosis in two MYCN-amplified neuroblastoma cell lines, SK-N-BE(2) and CHP134. Inhibition of both cell migration and invasion of extracellular matrix were also observed after ABCE1 suppression. Quantification of total protein levels indicated that ABCE1 suppression does not affect global protein synthesis, suggesting ABCE1 may instead translationally up-regulate specific proteins that are particularly important to neuroblastoma. These results show that ABCE1 is needed for the survival and motility of MYCN-amplified neuroblastoma cells and highlights the importance of further investigations into the potential of ABCE1 as a therapeutic target for this disease.
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