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Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Collins, RJ, Morgan, LD, Owen, S, Ruge, F, Jiang, WG ORCID: https://orcid.org/0000-0002-3283-1111 and Sanders, AJ ORCID: https://orcid.org/0000-0002-7997-5286 2018. Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis. International Journal of Cancer 143 (10) , pp. 2537-2550. 10.1002/ijc.31786

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Abstract

EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumour suppressive function in cancer. EPLIN expression was evaluated in prostate cancer cell lines and tissues. PC‐3 and LNCaP EPLINα overexpression models were generated through transfection with EPLINα sequence and EPLIN knockdown was achieved using shRNA in CA‐HPV‐10 cells. Functional assays were performed to evaluate cellular characteristics and potential mechanisms were evaluated using a protein microarray, and validated using western blot analysis. EPLIN expression was reduced in clinical prostate cancer sections, including hyperplasia (p≤0.001) and adenocarcinoma (p=0.005), when compared to normal prostate tissue. EPLINα overexpression reduced cell growth, migration and invasion, and influenced transcript, protein and phosphoprotein expression of paxillin, FAK and Src. EPLIN knockdown increased the invasive and migratory nature of CA‐HPV‐10 cells and also induced changes to FAK and Src total and/or phospho expression. Functional characterisation of cellular migration and invasion in addition to FAK and Src inhibition demonstrated differential effects between control and EPLINα overexpression and EPLIN knockdown cell lines. This study highlights that EPLIN expression in prostate cancer is able to influence several aspects of cancer cell characteristics, including cell growth, migration and invasion. The mechanism of the tumour suppressive action of EPLIN remains to be fully elucidated; and this study proposes a role for EPLIN's ability to regulate the aggressive characteristics of prostate cancer cells partially through regulating FAK/Src signalling.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Wiley
ISSN: 0020-7136
Funders: Cancer Research Wales
Date of First Compliant Deposit: 16 August 2018
Date of Acceptance: 24 July 2018
Last Modified: 13 Nov 2023 18:18
URI: https://orca.cardiff.ac.uk/id/eprint/114164

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