Emerging roles of the cellular prion protein (PrPC) and 37/67 kDa laminin receptor (RPSA) interaction in cancer biology

Abstract

The cellular prion protein (PrPC) is well-known for its involvement, under its pathogenic protease-resistant form (PrPSc), in a group of neurodegenerative diseases, known as prion diseases. PrPC is expressed in nervous system, as well as in other peripheral organs, and has been found overexpressed in several types of solid tumors. Notwithstanding, studies in recent years have disclosed an emerging role for PrPC in various cancer associated processes. PrPC has high binding affinity for 37/67 kDa laminin receptor (RPSA), a molecule that acts as a key player in tumorigenesis, affecting cell growth, adhesion, migration, invasion and cell death processes. Recently, we have characterized at cellular level, small molecules able to antagonize the direct PrPC binding to RPSA and their intracellular trafficking. These findings are very crucial considering that the main function of RPSA is to modulate key events in the metastasis cascade. Elucidation of the role played by PrPC/RPSA interaction in regulating tumor development, progression and response to treatment, represents a very promising challenge to gain pathogenetic information and discover novel specific biomarkers and/or therapeutic targets to be exploited in clinical settings. This review attempts to convey a detailed description of the complexity surrounding these multifaceted proteins from the perspective of cancer hallmarks, but with a specific focus on the role of their interaction in the control of proliferation, migration and invasion, genome instability and mutation, as well as resistance to cell death controlled by autophagic pathway.

Physiology of Cellular Prion Proteins in Reproduction

“…Recently, it emerged that PrP C is involved in various disease such as cancer and Alzheimer’s disease. The high level of PrP C drives the proliferation in cancer cells and growth the xenografted tumor via PI3/AKT signaling pathway and cyclin D expression in a cancer cell type-dependent manner ( Liang et al, 2007 ; Limone et al, 2023 ). PrP C interacts with various Alzheimer’s disease-related proteins such as amyloid- β oligomers (A β O) which accumulation is cause of an early toxic event ( Dohler et al, 2014 ).…”

The Multifaceted Functions of Prion Protein (PrPC) in Cancer

“…Moreover, PrP C has been shown to promote multidrug resistance in gastric cancer cells by inhibiting apoptosis [31]. Due to its ability to bind to certain extracellular matrix and adhesive proteins, PrP C exhibits an adhesive feature, indicating its involvement in cell adhesion [33,37,76]. A comparison of the PrP C expression in primary and metastatic sites was conducted in patients with metastatic and non-metastatic gastric cancer [34].…”