Effect of hypoxia on HIF-1a binding genes in SUM159 breast cancer cells with ChIP-Seq.
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 ß3 (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. Overall design: ChIP-seq for HIF-1a in SUM159 cells. Comparative HIF-1a binding gene profiling analysis of ChIP-seq data for SUM159 cells that were exposed in 20% or 1% oxygen condition for 16 hours.