YBX1 in Breast Cancer: From Molecular Mechanisms to Therapeutic Opportunities

Breast cancer, a heterogeneous malignancy with high metastatic potential, remains a global health burden. The Y-box binding protein 1 (YBX1), a multifunctional nucleic acid-binding protein, has emerged as a pivotal regulator in breast cancer progression, mediating Epithelial-Mesenchymal Transition (EMT), Cancer Stem Cell (CSC) maintenance, and therapeutic resistance. This review synthesizes preclinical and clinical evidence from 2023–2025, detailing YBX1’s structural features, molecular mechanisms in tumorigenesis, prognostic/diagnostic significance, and emerging therapeutic strategies. Data from 12+ cohorts (n > 2,500) demonstrate that high YBX1 expression correlates with poor survival (HR = 2.15, P < 0.001) and treatment resistance. Targeting YBX1 via small molecules, RNA therapies, and immune combinations shows promise in preclinical models, highlighting its potential as a precision oncology target.