Hepatitis A virus cellular receptor 1 (HAVcr-1) initiates prostate cancer progression in human cells via hepatocyte growth factor (HGF)-induced changes in junctional integrity

Telford, Emily A., Sanders, Andrew J. ORCID: https://orcid.org/0000-0002-7997-5286, Owen, Sioned, Ruge, Fiona, Harrison, Gregory M., Jiang, Wen G. ORCID: https://orcid.org/0000-0002-3283-1111 and Martin, Tracey A. ORCID: https://orcid.org/0000-0003-2690-4908 2022. Hepatitis A virus cellular receptor 1 (HAVcr-1) initiates prostate cancer progression in human cells via hepatocyte growth factor (HGF)-induced changes in junctional integrity. Biomolecules 12 (2) , 338. 10.3390/biom12020338

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Abstract

Background: HAVcR-1 has been linked to cancer aetiology and may regulate junctional complexes, with its role in prostate cancer still unexplored. This study aims to investigate the expression of HAVcR-1 in prostate cancer samples and the exploration of the cellular/molecular impact of HAVcR-1. Methods: Levels of HAVcR-1 ectodomain in the serum of prostate cancer patients were compared to healthy controls, and assessed as the total protein and gene expression of HAVcR-1 and tissues sections. The manipulation of HAVcR-1 levels within prostate cancer cell lines determined changes in cell behaviour using in vitro cell models and barrier function assays. Protein/phosphoprotein levels were assessed using Western blotting. Results: Levels of HAVcR-1 ectodomain from serum were decreased in patients with prostate cancer. Ectodomain levels correlated with the Gleason score. Histologically, the total protein/gene expression of HAVcR-1 was overexpressed in prostate cancer. The overexpression of HAVcR-1 in prostate cancer cell lines resulted in key changes in cell behaviour and the phosphorylation of β-catenin with a concurrent decrease in membranous E-cadherin, increased nuclear β-catenin and increased cyclin D1 protein expression, which were associated with HGF-promoted changes in the barrier function. Conclusions: HAVcR-1 expression and ectodomain release coincides with the presence of prostate cancer; thus, indicating HAVcR-1 as a potential biomarker to aid in diagnostics, and implicating HAVcR-1 in the dysregulation of junctional complexes.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Publisher:	MDPI
ISSN:	2218-273X
Funders:	Cancer Research Wales, grant number Martin102014.
Date of First Compliant Deposit:	24 February 2022
Date of Acceptance:	17 February 2022
Last Modified:	11 Oct 2023 21:33
URI:	https://orca.cardiff.ac.uk/id/eprint/147782

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