title: Plakophilin-associated RNA-binding proteins in prostate cancer and their implications in tumor progression and metastasis.
abstract: Both plakophilins (PKP) 1 and 3 play a role in the progression of prostate cancer. The RNA-binding proteins (RBPs) GAP-SH3-binding protein (G3BP), fragile-X-related protein 1 (FXR1), poly(A)-binding protein, cytoplasmic 1 (PABPC1), and up-frameshift factor 1 (UPF1) are associated with PKP3. All these RBPs have an impact on RNA metabolism. Until recently, the PKP-associated RBPs have not been analyzed in prostate cancer. In the current study, we showed by affinity purification that the PKP3-associated RBPs were also binding partners of PKP1. We examined the expression of PKP1/3-associated RBPs and PKP1/3 in prostate cell lines, tumor-free prostate, and 136 prostatic adenocarcinomas by immunofluorescence and immunoblot. All four RBPs G3BP, FXR1, UPF1, and PABPC1 were expressed in the glandular epithelium of the normal prostate. PKP1 and FXR1 were strongly reduced in tumor tissues with Gleason score >7 and diminished expression of PKP1 and FXR1 also appeared to be associated with a metastatic phenotype. Additionally, the predominant nuclear localization of UPF1 in normal glandular cells and low grade tumors was switched to a more cytoplasmic pattern in carcinomas with Gleason score >7. Our findings suggest that PKP1 and FXR1 may have a tumor-suppressive function and are downregulated in more aggressive tumors. Collectively, PKP1/3-associated RBPs FXR1 and UPF1 may have a functional role in prostate cancer progression and metastasis and highlight the potential importance of posttranscriptional regulation of gene expression and nonsense-mediated decay in cancer.
authors.affiliation: Division of Vascular Oncology and Metastasis, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
authors.forename: Philipp
authors.initials: P
authors.lastname: Ströbel
authors.forename: Alexander
authors.initials: A
authors.lastname: Marx
authors.forename: Ilse
authors.initials: I
authors.lastname: Hofmann
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology / Q000556:secondary; D001932:Brain Neoplasms / Q000503:physiopathology / Q000556:secondary; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D004265:DNA Helicases; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D051191:Plakophilins / Q000502:physiology*; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000502:physiology; D000075223:Poly-ADP-Ribose Binding Proteins; D011471:Prostatic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C096916:FXR1 protein, human; C495335:PKP1 protein, human; C495339:PKP3 protein, human; D051191:Plakophilins; D039122:Poly(A)-Binding Protein I; D000075223:Poly-ADP-Ribose Binding Proteins; D000067776:RNA Recognition Motif Proteins; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C101828:UPF1 protein, human