RelB Drives Integrin-Mediated Stress Tolerance and Relapse in High-Grade Serous Ovarian Cancer

NF-κB signaling, previously shown to enhance stemness traits, was investigated for its role in post-treatment tumor regrowth. Here, we found that NF-κB subunits RelA and RelB jointly regulate extracellular matrix genes but differentially control integrin subunits: RelA regulates ITGAV (αV) and RelB regulates ITGB3 (β3).

Integrin αVβ3 expression is upregulated on CSCs and this is partially driven by NF-κB activation. In vivo models demonstrate that αVβ3⁺ cells have higher tumor-initiating capacity and comprise over 90% of cells from relapsed tumors. Cells expressing RelB and αVβ3 preferentially grow on mesentery at relapse.