The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation.

Elisabeth Jahny,Thomas Knösel,Beatrix Jahnke,Daniela E Aust,Franziska Lademann,Axel Denz,Hai Yang,Petra Rümmele,Christian Pilarsky,Robert Grützmann,Bin Liu

doi:10.1371/journal.pone.0170390

Abstract

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest tumors worldwide. Understanding the function of gene expression alterations is a prerequisite for developing new strategies in diagnostic and therapy. GPRC5A (RAI3), coding for a seven transmembrane G protein-coupled receptor is known to be overexpressed in pancreatic cancer and might be an interesting candidate for therapeutic intervention. Expression levels of RAI3 were compared using a tissue microarray of 435 resected patients with pancreatic cancer as well as 209 samples from chronic pancreatitis (CP), intra-ductal papillary mucinous neoplasm (IPMN) and normal pancreatic tissue. To elucidate the function of RAI3 overexpression, siRNA based knock-down was used and transfected cells were analyzed using proliferation and migration assays. Pancreatic cancer patients showed a statistically significant overexpression of RAI3 in comparison to normal and chronic pancreatitis tissue. Especially the loss of apical RAI3 expression represents an independent prognostic parameter for overall survival of patients with pancreatic cancer. Suppression of GPRC5a results in decreased cell growth, proliferation and migration in pancreatic cancer cell lines via a STAT3 modulated pathway, independent from ERK activation.

Highlights

Pancreatic cancer is one of the most perilous and lethal solid malignancies and the five-year relative survival rate, is one of the lowest for all cancers with 8% [1]
Pancreatic Ductal Adenocarcinoma (PDAC)-tissue showed an obvious loss of apical expression (Fig 1A–1F and Fig 2A and 2B) (Kruskal-Wallis-test p
The results in Tissue microarray (TMA) show clearly, that retinoic acidinducible 3 (RAI3)/GPRC5a is over-expressed in PDAC in comparison to normal pancreas or chronic pancreatitis (CP) tissue

Summary

Introduction

Pancreatic cancer is one of the most perilous and lethal solid malignancies and the five-year relative survival rate, is one of the lowest for all cancers with 8% [1]. RAI3 in Pancreatic Cancer decision to publish, or preparation of the manuscript

Methods

Results

Conclusion