The nucleo-junctional interplay of the cellular prion protein: A new partner in cancer-related signaling pathways?. Issue 2 (3rd March 2016)

• Record Type: Journal Article
• Authors: Rousset, Monique; Leturque, Armelle; Thenet, Sophie
• Is Part Of: Prion. Volume 10:Issue 2(2016)
• Page Start: 143
• Page End: 152
• Publication Date: 2016-03-03
• Subjects: (10 max) Prion protein -- β-catenin -- cancer -- desmosomes -- epithelial-mesenchymal transition -- nucleus -- Src kinase -- nucleus -- Wnt signaling -- YAP -- γ-catenin; Protein folding -- Periodicals; Prions -- Periodicals; Proteins -- Biotechnology -- Periodicals; 572.633
• DOI: 10.1080/19336896.2016.1163457
• Languages: English
• ISSNs: 1933-6896

Abstract

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.