E-Poster Presentation ESA-SRB-ANZBMS 2021

Role of the prorenin receptor in endometrial cancer cell growth (#64)

Jacinta H Martin 1 , Riazuddin Mohammed 1 , David A Skerrett-Byrne 2 , Sarah J Delforce 1 , Celine Corbisier 1 , Juhura G Almazic 1 3 , Nicole M Verrills 4 , Andrew N Stephens 5 , Evdokia Dimitriadis 6 , Yu Wang 1 , Eugenie R Lumbers 1 , Kirsty G Pringle 1
  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, NSW, Australia
  3. School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia
  4. 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
  5. Hudson Institute of Medical Research and Department of Molecular and Translational Sciences,, Monash University, , Clayton, New South Wales, Australia
  6. Gynaecology Research Centre, , University of Melbourne; The Women’s Hospital,, Melbourne, Victoria, Australia

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in women after breast, lung and colorectal cancer. Despite numerous scientific advances, the incidence and mortality rate of endometrial cancer continues to rise. Considerable research effort has been placed on understanding the pathogenesis of this disease. Emerging evidence now suggests a putative role of the (pro)renin receptor ((P)RR), in the ontogenesis of endometrial cancer. Support for this notion arises from literature implicating the (P)RR in breast cancer and pancreatic carcinoma pathophysiology by virtue of its role in proliferation, angiogenesis, fibrosis, migration and invasion.

In view of these data, we aimed to investigate the functional role of the (P)RR in human endometrial cancer progression and development. To this end, we employed an siRNA-mediated knockdown approach to abrogate (P)RR expression in the immortalized endometrial epithelial cell lines; Ishikawa, AN3 CA and HEC-1-A and examined cellular proliferation and cellular viability. To further extend these analyses 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 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 in the treatment of this cancer.