Figure 1.

Cellular prion protein (PrP^C) as a main regulator of CSCs phenotype, biology, and functioning. The left panel of the cartoon depicts the cross-talk between cancer stem cells (CSCs) and major cellular components (i.e., endothelial cells, fibroblasts, pericytes, macrophages, and T cells) of the tumor micro-environment (TME). The right panel schematizes the role of PrP^C in promoting CSC self-renewal, proliferation, and migration. In addition, PrP^C interacts with several receptors and cell surface proteins to modulate CSCs’ tumor-initiating and metastatic capacities, while promoting increased therapeutic resistance. In this way, it modulates tumor growth, survival, infiltration, and multi-drug resistance.