title: The nucleo-junctional interplay of the cellular prion protein: A new partner in cancer-related signaling pathways?
abstract: The cellular prion protein PrP(c) plays important roles in proliferation, cell death and survival, differentiation and adhesion. The participation of PrP(c) in tumor growth and metastasis was pointed out, but the underlying mechanisms were not deciphered completely. In the constantly renewing intestinal epithelium, our group demonstrated a dual localization of PrP(c), which is targeted to cell-cell junctions in interaction with Src kinase and desmosomal proteins in differentiated enterocytes, but is predominantly nuclear in dividing cells. While the role of PrP(c) in the dynamics of intercellular junctions was confirmed in other biological systems, we unraveled its function in the nucleus only recently. We identified several nuclear PrP(c) partners, which comprise γ-catenin, one of its desmosomal partners, β-catenin and TCF7L2, the main effectors of the canonical Wnt pathway, and YAP, one effector of the Hippo pathway. PrP(c) up-regulates the activity of the β-catenin/TCF7L2 complex and its invalidation impairs the proliferation of intestinal progenitors. We discuss how PrP(c) could participate to oncogenic processes through its interaction with Wnt and Hippo pathway effectors, which are controlled by cell-cell junctions and Src family kinases and dysregulated during tumorigenesis. This highlights new potential mechanisms that connect PrP(c) expression and subcellular redistribution to cancer.
authors.affiliation: a Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|b INSERM, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|c Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;
authors.forename: Monique
authors.initials: M
authors.lastname: Rousset
authors.affiliation: a Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|b INSERM, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|c Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;
authors.forename: Armelle
authors.initials: A
authors.lastname: Leturque
authors.affiliation: a Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|b INSERM, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|c Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers , Paris , France ;|d EPHE, PSL Research University, Laboratoire de Pharmacologie Cellulaire et Moléculaire , Paris , France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Thenet
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D003896:Desmosomes / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D000090683:Hippo Signaling Pathway; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018621:PrPC Proteins / Q000032:analysis / Q000378:metabolism*; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D018621:PrPC Proteins; D017346:Protein Serine-Threonine Kinases
keywords: (10 max) Prion protein; Src kinase; Wnt signaling; YAP; cancer; desmosomes; epithelial-mesenchymal transition; nucleus; β-catenin; γ-catenin