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Effect of hypoxia on HIF-1α binding genes in MDA231-BrM2 breast cancer brain-selective metastatic cells with ChIP-Seq.

GSE268802 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/05/15 Platform GPL24676
Summary
Brain metastasis is a major cause of breast cancer mortality, but the molecular basis and pathological mechanisms are poorly understood. Here, we determined that integrin β3 (ITGB3) expression mediated by hypoxia-inducible factor 1 (HIF-1) plays a critical role in brain metastasis of breast cancer. Hypoxia induces HIF-1-dependent expression of ITGb3, which is required for breast cancer cell migration and invasion. Knockdown of HIF-1a or ITGB3 expression impairs the colonization of breast cancer cells to brain after injection into the cardiac left ventricle. Mechanistically, ITGB3 protein expressed by breast cancer cells was incorporated into extracellular vesicles (EVs). The ITGb3+ EVs associated with brain endothelial cells, activated vascular endothelial growth factor receptor 2 signaling, and increased endothelial permeability to facilitate metastatic colonization of the brain.
Published in
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles
Yang Y, Chen C, Lyu Y et al. · The Journal of clinical investigation 2025 · PMID 40662366 · doi:10.1172/JCI190470
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Also filed as BioProject PRJNA1118770 and SRA study SRP511065. Searching any of these in the dataset finder brings you back here.

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