High-throughput screening for novel regulators of Beta-catenin in Wnt signalling

Lloyd-Lewis, Bethan 2011. High-throughput screening for novel regulators of Beta-catenin in Wnt signalling. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Beta-catenin is a crucial component of the Wnt signalling pathway, which is imperative in many developmental processes and aberrantly regulated in several different cancers. The standard model of Wnt/Beta-catenin signalling states that, upon stimulation by Wnt ligand, Beta-catenin accumulates and subsequently translocates to the nucleus to activate TCF-dependent transcription of a variety of target genes, including oncogenes. However, the mechanisms regulating the nuclear localisation of Beta-catenin and its correlation with TCF-dependent transcription are poorly understood. In order to identify novel regulators of Beta-catenin levels and localisation in Wnt signalling imaging-based high-throughput knockout screens were developed in a Wnt inducible cell line, in addition to a cancer cell line in the presence of normal and downregulated APC. Results from the screens show that, in addition to known Wnt signalling components, genes not previously ascribed to the pathway appeared to modulate Beta-catenin. The study has provided sources of possible mechanistic insights into a number of areas of biology that may be involved in β-catenin regulation. Furthermore, it reveals an unprecedented degree of cross talk between Wnt and many other major signalling pathways. Moreover, the data indicated a degree of cell-type specificity in the regulators identified and, significantly, a lack of correlation between β-catenin levels and transcriptional activity.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Funders:	Cancer Research UK
Date of First Compliant Deposit:	30 March 2016
Last Modified:	04 Feb 2025 16:16
URI:	https://orca.cardiff.ac.uk/id/eprint/24229

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