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 ORCID: 0000-0002-7997-5286, Owen, Sioned, Ruge, Fiona, Harrison, Gregory M., Jiang, Wen G. and Martin, Tracey A. (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). ART 338. doi: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
Article Type:	Article
Uncontrolled Keywords:	HAVcR-1; Junctions; Metastasis; Migration; Prognosis; Prostate cancer
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Schools and Research Institutes > School of Education and Science
Research Priority Areas:	Place, Environment and Community
Depositing User:	Susan Turner
Date Deposited:	27 Jul 2022 14:23
Last Modified:	31 Aug 2023 08:57
URI:	https://eprints.glos.ac.uk/id/eprint/11399

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