Investigating the Novel Oncogenic Function of SAPCD2 in Pediatric Neuroblastoma
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Pediatric neuroblastoma is the most common extra-cranial solid malignancy in infants and children. It is an aggressive neuroendocrine cancer that circumvents the normal differentiation process of sympathetic neuronal precursors into diverse cell types of the peripheral nervous system. SAPCD2 is a newly identified cell cycle-associated gene involved in mitotic progression and spindle assembly. Although the specific mechanism by which SAPCD2 modulates the cell cycle is poorly understood, its function appears to be most critical in early embryonic development where it regulates cell polarization, orientation, and fetal tissue segmentation. The expression of SAPCD2 is generally low or absent in healthy postnatal tissues, yet its abnormal restored expression in several adult cancers has been well documented and its oncogenic function has been supported by in vitro and in vivo investigations. Its relevance to neuroblastoma, however, has never been investigated. The objective of this thesis work is to determine whether high expression of SAPCD2 in neuroblastoma correlates with poor patient survival and, if so, to characterize its oncogenicity in vitro utilizing human neuroblastoma cell lines. Our results indicate that SAPCD2 functions as an oncogene in pediatric neuroblastoma that contributes to poor overall and recurrence-free survival. This effect likely results from the cellular effects that SAPCD2 possesses on neuronal precursors, including sustained proliferative signaling and evasion of growth suppressors. However, SAPCD2 does not appear to play a significant role in inducing the differentiation of neuronal precursors. In the future, studies aimed at characterizing the effect of SAPCD2 on coordinating apoptotic pathways would complement the results of our current investigation and enrich the understanding of the role that SAPCD2 plays in tumorigenesis.