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The role of the COPII complex in neuroblastoma differentiation by N2-Src

Hernandez Perez, Ines (2015) The role of the COPII complex in neuroblastoma differentiation by N2-Src. MSc by research thesis, University of York.

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Abstract

Neuroblastoma is a childhood cancer of the developing nervous system caused by dysregulated proliferation of neural crest cells. Differentiation agents are used as standard treatment to induce the regression of neuroblastoma tumours. The ability of some neuroblastomas to spontaneously differentiate correlates with a high expression of the neuronal tyrosine kinase N2-Src. Furthermore, N2-Src is able to induce differentiation of neuroblastoma cell lines, providing insights for novel differentiation treatments. Our laboratory generated preliminary data suggesting that N2-Src overexpression increases tyrosine phosphorylation of a complex that includes proteins of the COPII coat. The COPII complex plays an essential role in the early secretory pathway by coordinating vesicle trafficking from the endoplasmic reticulum to the Golgi apparatus. In this study I investigated the role of the COPII complex in neuroblastoma differentiation downstream of N2-Src. Our hypothesis is that tyrosine phosphorylation of COPII coat components by N2-Src directs the transport of cargoes that promote differentiation of neuroblastoma cells. I demonstrated that N2-Src interacts with different components of the COPII complex, and that the overexpression of N2-Src specifically increases tyrosine phosphorylation of the COPII coat component Sec23A in HeLa cells. Interestingly, overexpressed N2-Src in COS7 cells is located in perinuclear endosomal structures and induces the redistribution of ER- exit sites, where the formation of COPII vesicles is initiated. Finally, I observed inhibition of N2-Src induced neurite outgrowth by the overexpression of COPII components in fibroblast and neuroblastoma cells. Together, these data implicate COPII traffic in N2-Src induced neuroblastoma differentiation and provide insight for the development of novel differentiation treatments.

Item Type: Thesis (MSc by research)
Academic Units: The University of York > Biology (York)
Depositing User: Ines Hernandez Perez
Date Deposited: 22 Oct 2015 15:28
Last Modified: 12 Oct 2017 00:18
URI: http://etheses.whiterose.ac.uk/id/eprint/10483

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