GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE334nnn/GSE334629/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE334629GEOGSEfalseRelB Drives Integrin-Mediated Stress Tolerance and Relapse in High-Grade Serous Ovarian CancerHigh-grade serous ovarian cancer (HGSOC) often relapses after chemotherapy due to chemoresistant cancer stem-like cells (CSCs). 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. Targeting this pathway, combined RelB knockdown and inhibition of αVβ3, eliminated stress-tolerant CSCs, reduced tumor burden, and extended survival. These findings highlight integrins as promising therapeutic targets and reveal distinct roles for NF-κB subunits in regulating metastasis and relapse in HGSOC.2026/06/10GSE334629GSM9792328GSM9792339GSM9792338GSM9792327GSM9792329GSM9792331GSM9792330GSM9792333GSM9792332GSM9792324GSM9792335GSM9792334GSM9792326GSM9792337GSM9792325GSM979233616791334629Homo sapiens