Loss of Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ) Promotes Prostate Cancer Metastasis

Abstract

Background:The role of pleiotrophin and its receptors RPTP␤/ and Syndecan-3 during tumor metastasis remains unknown. Results: RPTP␤/ knockdown initiates EMT, promotes pleiotrophin-mediated migration and attachment through Syndecan-3 and induces in vivo metastasis. Conclusion: RPTP␤/ plays a suppressor-like role in prostate cancer metastasis. Significance: Boosting RPTP␤/ or attenuating Syndecan-3 signaling pathways may lead to more effective therapeutic strategies in treating prostate cancer metastasis.

Hypothalamic proteoglycan syndecan-3 is a novel cocaine addiction resilience factor

“…While syndecan-3 is a co-receptor for certain ligands and enhances the formation of their receptor-signaling complexes4, our findings demonstrate another role of syndecan-3 as an alternative GDNF receptor that counterbalances the effects of GDNF on its high-affinity receptor complex, GFR-α1/c-Ret. The syndecan-3 ligand pleiotrophin has been recently shown to exert differential actions on prostate cells acting through syndecan-3 or its conventional receptor RPTβ/ζ7. Thus, syndecan-3 may have a general role counterbalancing the effects of some of its ligands on their conventional receptors.…”

“…However, few, if any, studies have identified addiction-resistant factors. Syndecans are cell-associated heparan sulfate proteoglycans characterized by cysteine-free extracellular domains that extend from the cell surface, allowing them to act as either co-receptors or alternative receptors for several peptides such as glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factors, pleiotrophin, midkine, vascular endothelial growth factors, and transforming growth factor-β, as well as extracellular matrix proteins like fibronectin and laminin4567. Four mammalian syndecans have been identified, of which syndecan-3, also known as N -Syndecan, is enriched in the brain4.…”

Receptor-type Protein-tyrosine Phosphatase ζ Is a Functional Receptor for Interleukin-34

“…Given the multiplicity of ligands for PTP-, the role of IL-34 regulation in these settings will need to be further defined. Also, our demonstration that IL-34 modulates tumorigenic properties of the glioblastoma cell line U251 coupled with the fact that PTP-is expressed in neuroblastomas (19) and other tumors (38,41) strongly suggests that analysis of the CSF-1R-dependent and -independent roles of IL-34 in tumorigenesis is of great translational medicine relevance.…”

“…5A). PTP-ligands have been shown to increase the tyrosine phosphorylation of FAK in lung and prostate carcinomas and endothelial cells (32,38,41) and of paxillin in osteoblastic cells (64), and G proteincoupled receptor kinase interactor 1/Cool-associated, tyrosinephosphorylated 1 (GIT1/Cat-1) has been shown to be a direct PTP-substrate (65). We showed that either PTN or IL-34 also increased the tyrosine phosphorylation of FAK (ϳ125 kDa), paxillin (ϳ70 kDa) (Fig.…”

RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas

“…MET encodes a well-studied proto-oncogene whose activation is triggered by dimerization of the intracellular domain upon binding of hepatocyte growth factor (HGF) (Stommel et al 2007;Li et al 2011). PTPRZ1 encodes a membrane-associated tyrosine phosphatase that is highly expressed in the central nervous system (Muller et al 2003) and signals through beta-catenin-mediated functions (Diamantopoulou et al 2012). The recurrent nature of the ZM fusion suggests that it plays an active role in GBM biology.…”