The Multifaceted Functions of Prion Protein (PrPC) in Cancer

Cancers (Basel). 2023 Oct 13;15(20):4982. doi: 10.3390/cancers15204982.

Abstract

The cellular prion protein (PrPC) is a glycoprotein anchored to the cell surface by glycosylphosphatidylinositol (GPI). PrPC is expressed both in the brain and in peripheral tissues. Investigations on PrPC's functions revealed its direct involvement in neurodegenerative and prion diseases, as well as in various physiological processes such as anti-oxidative functions, copper homeostasis, trans-membrane signaling, and cell adhesion. Recent findings have revealed the ectopic expression of PrPC in various cancers including gastric, melanoma, breast, colorectal, pancreatic, as well as rare cancers, where PrPC promotes cellular migration and invasion, tumor growth, and metastasis. Through its downstream signaling, PrPC has also been reported to be involved in resistance to chemotherapy and tumor cell apoptosis. This review summarizes the variance of expression of PrPC in different types of cancers and discusses its roles in their development and progression, as well as its use as a potential target to treat such cancers.

Keywords: cancer; drug resistance; prion protein (PrPC); therapeutic target.

Publication types

  • Review

Grants and funding

The authors acknowledge the following sources of funding: Institut National de la Santé et de la Recherche Médicale (INSERM), University Grenoble-Alpes, VALO-GRAL CBH-EUR-GS (ANR-17-EURE-0003), Région Auvergne-Rhône-Alpes/Cancéropôle Lyon Au-vergne Rhône-Alpes, Ligues Départementales (Isère & Savoie) contre le Cancer, ARC (association de recherche contre le cancer) (ARCPJ2021050003618) and Fondation pour la Recherche Médicale (FRM) SPF20150934074. Part of this work has been performed at the CMBA platform—IRIG-DS-BGE-Gen&Chem-CMBA, CEA-Grenoble, F-38054 Grenoble, (a member of GIS-IBISA and ChemBioFrance infrastructure) supported by GRAL, a program of the Chemistry Biology Health Graduate School of Université Grenoble Alpes (ANR-17-EURE-0003).