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Functional role of Epithelial Protein Lost in Neoplasm (EPLIN) in prostate cancer metastasis

Collins, Ross J. 2017. Functional role of Epithelial Protein Lost in Neoplasm (EPLIN) in prostate cancer metastasis. PhD Thesis, Cardiff University.
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Abstract

Prostate cancer is the second most common cancer in the UK and incidence is gradually rising. Prostate cancer has a specific tendency to establish bone metastases, and this process significantly affects patient mortality and morbidity. This PhD evaluates the importance of EPLIN in the development and progression of prostate cancer, aims to explore any relevance of EPLIN in the establishment of bone metastases and to clarify the functional and mechanistic implications governing EPLIN biology in prostate cancer. EPLIN expression was established in clinical prostate cancer tissue and prostate cancer cell lines and revealed a downregulation or loss of EPLIN in more aggressive cancer phenotypes. Importantly, EPLIN was abolished in clinical cancer sections including hyperplasia and adenocarcinoma, in addition to being markedly lost in aggressive cell lines PC-3, LNCaP and VCaP. Subsequently, EPLINα, the main isoform linked to cancer progression, was overexpressed in PC-3 and LNCaP cells lines to explore the functional significance of EPLINα at a cellular level. In vitro functional analyses revealed EPLINα is able to influence several tumour cell characteristics. EPLINα overexpression reduced cell proliferation, migration and invasion, and was able to increase cellular adhesion, when compared to control cell lines. EPLINα expression was also explored in an in vitro bone environment via culturing cells with Bone Matrix Extract solution, and also using a co-culture method with human osteoblasts. To establish the mechanism of action of EPLINα in prostate cancer progression, the EPLIN interactome was evaluated, identifying several key molecular associations.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Medicine
Date of First Compliant Deposit: 31 July 2017
Last Modified: 30 Jan 2019 02:30
URI: http://orca.cf.ac.uk/id/eprint/103089

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