Integrated control of cancer stemness by σ₁ receptor in advanced prostate cancer.

ABSTRACT: Cancer stem cells (CSCs) are pervasively present in human cancers and have a fundamental role in treatment failure and disease recurrence. Identifying critical elements that sustain the CSC phenotype may lead to novel strategies for cancer treatment. Here, we provide evidence of an essential link between the σ₁ receptor (σ₁R), a ligand-regulated chaperone protein residing preferentially at the endoplasmic reticulum-mitochondria contact sites, and CSCs in castration-resistant prostate cancers (CRPCs). Integrating functional assays in multiple preclinical models with transcriptomic and proteomic data, we found that σ₁R controls CSC self-renewal capacity and tumorigenic proficiency by coordinating mitochondrial dynamics and mitochondrial-nuclear signaling. Inh

SUBMITTER: Civenni G 

PROVIDER: S-EPMC12518131 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature