Oncotarget

Research Papers:

Role of the prorenin receptor in endometrial cancer cell growth

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 and Kirsty G. Pringle _

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Abstract

Jacinta H. Martin1,*, Riazuddin Mohammed1,*, Sarah J. Delforce1, David A. Skerrett-Byrne2, Celine Corbisier de Meaultsart1, Juhura G. Almazi3,4, Andrew N. Stephens5,6, Nicole M. Verrills3, Evdokia Dimitriadis7, Yu Wang1, Eugenie R. Lumbers1 and Kirsty G. Pringle1

1 School of Biomedical Sciences and Pharmacy, Priority Research Centre for Reproductive Science, Mothers and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia

2 School of Environmental and Life Sciences, Priority Research Centre for Reproductive Science, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia

3 School of Biomedical Sciences and Pharmacy, Priority Research Centre for Cancer Research, Innovation and Translation, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia

4 School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia

5 Hudson Institute of Medical Research, Clayton, Victoria, Australia

6 Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia

7 Department of Obstetrics and Gynaecology, Gynaecology Research Centre, The Women’s Hospital, University of Melbourne, Melbourne, Victoria, Australia

* These authors contributed equally to this work

Correspondence to:

Kirsty G. Pringle, email: kirsty.pringle@newcastle.edu.au

Keywords: (P)RR; ATP6AP2; endometrial cancer; cellular viability; cellular proliferation

Received: January 20, 2022     Accepted: March 14, 2022     Published: April 01, 2022

Copyright: © 2022 Martin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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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