N-MYC Transcription Factor Increases the Expression of Alpha-7 Nicotinic Acetylcholine Receptor Promoting Cell Viability in Neuroblastoma Cell Line

Abstract

Neuroblastoma is the most common extracranial solid tumor in children. It accounts for more than 7% of malignancies in patients less than fifteen years of age and makes up 15% of oncology deaths. Neuroblastoma is a cancer derived from primordial neural crest cells under conditions of inappropriate migration, maturation, and or differentiation. These extracranial tumors are formed in the adrenal medulla, sympathetic ganglia, and abdomen. Current treatments for neuroblastoma include surgery, chemotherapy, radiotherapy, and biotherapy. Interestingly, neuroblastoma tumors are heterogenous with some children having low-risk tumors that regress entirely while others have high-risk tumors with widespread metastasis and poor outcomes. The expression of MYCN, a gene in a family of oncogenic drivers, in neuroblastoma tumors has been associated with high-risk neuroblastoma and worse outcomes. Children with high-risk neuroblastoma account for approximately half of all patients diagnosed with neuroblastoma. Despite current interventions and aggressive treatment, children with high-risk neuroblastoma have a long-term survival rate of less than 50%. Currently, there are not many targeted therapies for high-risk neuroblastoma as there is little know about the mechanism driving this cancer. By identifying the mechanism driving tumor progression, a treatment to specifically target the different steps of this cancer can be created. Signaling through neuronal nicotinic acetylcholine receptors (nAChRs) is involved in many neuronal processes of neural tissue, including the proliferation of neural crest cells. These receptors are a diverse group of ligand-gated pentametric channels can exist as homopentamers or heteropentamers of α or β subunits. The only mammalian homopentamer is the α7 receptor that when activated is suggested to promote neural cell survival. Furthermore, expression of nAChR has been shown to be regulated by MYCN. Our lab is interested to see if MYCN-expressing neuroblastoma tumors upregulate the expression of nAChRs leading to an overall drive in tumor progression. Therefore, targeting this interaction between nAChRs and MYCN can become a potential therapy of high-risk neuroblastoma.