The characterisation of genes from a genetic screen that promote invasion

Taylor, Louisa (2018) The characterisation of genes from a genetic screen that promote invasion. MRes thesis, University of Nottingham.

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Abstract

Metastasis accounts for over 90% of cancer mortality. The first step of metastasis is the invasion of cancer cells into the tissue and vasculature surrounding the tumour. Despite its clinical importance, our understanding of invasion and its genetic determinants is limited. A large-scale, loss-of-function genetic screen in Drosophila melanogaster has recently been completed in the Georgiou Lab which identified a number of genes that may promote cellular invasion upon their depletion in the Drosophila epithelium. This project will focus on the characterisation of some of these hits.

Glioblastoma multiforme is the most frequent and invasive primary tumour of the central nervous system. Using the human U87 glioblastoma cell line, human orthologs of a number of the aforementioned invasive hits were studied in in vitro invasion assays. Knockdown of two of the tested genes, TSNAX and JAG1, reduced the invasive capacity of U87 glioblastoma cells and hence could represent targets for further research in glioblastoma invasion.

Gtp-bp is a gene implicated in co-translational protein targeting that was identified as possessing pro-invasive capabilities when depleted in the genetic screen. Prior to this study, a potential role for the gene in cell fate decisions was also revealed. In this project, the effect of Gtp-bp on cell fate decisions and cell specification was further explored using the Drosophila posterior midgut as a model system. Adult posterior midguts deficient for Gtp-bp show severe disruption of tissue homeostasis and a marked reduction in stem cell abundance. Further to this, depletion of Gtp-bp activity in the midgut results in an apparent reduction of the enterocyte population, likely due to defective differentiation. The results obtained here suggest that Gtp-bp plays an important role in intestinal stem cell maintenance and possibly differentiation, providing evidence for novel roles of co-translational protein targeting in tissue homeostasis and cell fate decisions.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Georgiou, Marios
Shaw, Peter
Subjects: R Medicine > RC Internal medicine > RC 254 Neoplasms. Tumors. Oncology (including Cancer)
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 49154
Depositing User: Taylor, Louisa
Date Deposited: 12 Jul 2018 04:40
Last Modified: 08 May 2020 09:00
URI: http://eprints.nottingham.ac.uk/id/eprint/49154

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