title: The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation.
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.
authors.affiliation: Department of Surgery, TU Dresden, Fetscherstraße 74, Dresden, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jahny
authors.affiliation: Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
authors.forename: Hai
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Surgery, TU Dresden, Fetscherstraße 74, Dresden, Germany.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Jahnke
authors.affiliation: Department of Surgery, TU Dresden, Fetscherstraße 74, Dresden, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Lademann
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-Universität München, München, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Knösel
authors.affiliation: Institute of Pathology, Universitätsklinikum Erlangen, Krankenhausstraße 8-10, Erlangen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Rümmele
authors.affiliation: Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.affiliation: Institute of Pathology, TU Dresden, Fetscherstraße 74, Dresden, Germany.
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Aust
authors.affiliation: Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
authors.forename: Christian
authors.identifier: http://orcid.org/0000-0002-7968-3283
authors.initials: C
authors.lastname: Pilarsky
authors.affiliation: Department of Surgery, Universitätsklinikum Erlangen, Krankenhausstraße 12, Erlangen, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Denz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: C116760:GPRC5A protein, human; D043562:Receptors, G-Protein-Coupled; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human