Role of the Prorenin Receptor in Endometrial Cancer Cell Growth

Overview

Journal Oncotarget

Specialty Oncology

Date 2022 Apr 11

PMID 35401936

Authors

Jacinta H Martin

Riazuddin Mohammed

Sarah J Delforce

David A Skerrett-Byrne

Celine Corbisier de Meaultsart

Juhura G Almazi

Andrew N Stephens

Nicole M Verrills

Evdokia Dimitriadis

Yu Wang

Eugenie R Lumbers

Kirsty G Pringle

Affiliations

Soon will be listed here.

Abstract

Endometrial cancer is the most diagnosed gynecological malignancy. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer continues to rise. Emerging evidence suggests a putative role of the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. The (P)RR is implicated in breast cancer and pancreatic carcinoma pathophysiology by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion. Thus, we aimed to investigate the functional role of the (P)RR in human endometrial cancer. We employed an siRNA-mediated knockdown approach to abrogate (P)RR expression in the endometrial epithelial cell lines; Ishikawa, AN3CA and HEC-1-A and examined cellular proliferation and viability. We also carried out a sophisticated proteomic screen to explore potential pathways via which the (P)RR is acting in endometrial cancer physiology. These data confirmed that the (P)RR is critical for endometrial cancer development, contributing to both its proliferative capacity and in the maintenance of cell viability. This is likely mediated through proteins such as MGA, SLC4A7, SLC7A11 or DHRS2, which were reduced following (P)RR knockdown. These putative protein interactions/pathways, which rely on the presence of the (P)RR, are likely to contribute to endometrial cancer progression and could therefore, represent several novel therapeutic targets for endometrial cancer.

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