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.

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.

• Authors: Emily A Telford, Andrew J Sanders, Sioned Owen, Fiona Ruge, Gregory M Harrison, Wen G Jiang, Tracey A Martin
• Journal: Biomolecules (Biomolecules) Vol. 12 Issue 2 (02 21 2022) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 35204839 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• HGF protein, human
• Hepatitis A Virus Cellular Receptor 1
• Receptors, Virus
• beta Catenin
• Hepatocyte Growth Factor

Topics

• Cadherins
• Cell Line, Tumor
• Hepatitis A Virus Cellular Receptor 1
• Hepatocyte Growth Factor
• Humans
• Intercellular Junctions (physiology)
• Male
• Prostatic Neoplasms (genetics)
• Receptors, Virus
• beta Catenin