Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Via Pansini 5, 80131, Naples, Italy.
Department of Health Sciences, University "Magna Graecia" of Catanzaro, Campus "S. Venuta", 88100, Catanzaro, Italy.
Cell Mol Life Sci. 2023 Jul 15;80(8):207. doi: 10.1007/s00018-023-04844-2.
The cellular prion protein (PrP) is well-known for its involvement, under its pathogenic protease-resistant form (PrP), in a group of neurodegenerative diseases, known as prion diseases. PrP 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 PrP in various cancer associated processes. PrP 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 PrP 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 PrP/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.
细胞朊病毒蛋白（PrP）以其在一组神经退行性疾病（称为朊病毒病）中的致病蛋白酶抗性形式（PrP）参与而闻名。PrP 在神经系统以及其他外周器官中表达，并在几种实体瘤中发现过度表达。尽管如此，近年来的研究揭示了 PrP 在各种与癌症相关的过程中出现的新作用。PrP 与 37/67 kDa 层粘连蛋白受体（RPSA）具有高结合亲和力，RPSA 是一种在肿瘤发生中起关键作用的分子，影响细胞生长、粘附、迁移、侵袭和细胞死亡过程。最近，我们在细胞水平上表征了能够拮抗 PrP 与 RPSA 直接结合的小分子及其细胞内运输。这些发现非常重要，因为 RPSA 的主要功能是调节转移级联中的关键事件。阐明 PrP/RPSA 相互作用在调节肿瘤发生、进展和对治疗的反应中的作用，代表了获得发病机制信息和发现新的特异性生物标志物和/或治疗靶点以在临床环境中利用的非常有前途的挑战。这篇综述试图从癌症特征的角度详细描述这些多方面蛋白的复杂性，但特别关注它们相互作用在控制增殖、迁移和侵袭、基因组不稳定性和突变以及由自噬途径控制的细胞死亡抗性方面的作用。
