Implications of cellular prion protein in tumor biology

Abstract

Prion proteins (PrP) are primarily known for their role in neurodegenerative conditions like Creutzfeldt-Jakob Disease, where the misfolded, pathogenic isoform PrPSc propagates by using the normal cellular prion protein, PrPc, as a template, leading to aggregation and neuronal death. PrPc is a widely expressed glycoprotein that, beyond its role in prion disease, has emerged in specific contexts as a modulator of several hallmark cancer processes, including proliferation, apoptosis resistance, cellular signaling, adhesion, survival, and motility. This paper explores current evidence on how PrPc, and its misprocessed isoform pro-PrP, contribute to tumor progression across multiple cancer types, using colorectal cancer (CRC) as a unifying disease model to integrate mechanisms that are otherwise dispersed across the literature. This review will examine PrPc’s role in sustaining proliferative signaling, resisting apoptosis, promoting migration and metastasis through its interaction with filamin A (FLNa), and contributing to therapy resistance. The goal is to consider the extent to which these mechanisms converge specifically in CRC, and what this means for PrPc’s potential as a diagnostic and therapeutic target.