Fig 2: Crosstalk of hypoxia-induced endothelial-mesenchymal transition (EndMT) signaling pathways. Under hypoxic conditions, transcription factor hypoxia inducible factor-1α (HIF-1α) protein is accumulated and functionally activated, which induces the expression of genes associated with EndMT, such as Notch1, transforming growth factor-β (TGF-β), and runt-related transcription factor 3 (RUNX3), and the stabilization of Snail and Slug. RUNX3 is likely to be a direct target of HIF-1α, which can stabilize the Notch-ICD. The Notch-ICD also promotes the expression of EndMT-associated genes. Hypoxia can also activate the TGF-β signaling pathway through Smad2/3 proteins to induce EndMT transcription factor expression. ICD, intracellular domain.