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. 2020 Oct 30;11:579552. doi: 10.3389/fimmu.2020.579552

Figure 2.

Figure 2

Superoxide dismutase-3 (SOD3)-induced pathways connecting vascular normalization and T-cell diapedesis in tumors. Perivascular SOD3 prevents nitric oxide (NO) oxidation, thus increasing EC NO levels. This causes PHD inhibition and the nuclear accumulation of HIF-2α. HIF-2α then initiates a transcriptional program that upregulates vascular-endothelial cadherin (VEC) and certain WNT ligands. Increased VEC levels reduce vascular permeability and normalize the vasculature. Autocrine WNT ligands activate the WNT pathway, which stabilizes β-catenin and FoxM1. β-catenin is sequestered in the juxtamembrane region by VEC, reinforcing AJs. FoxM1 translocates to the nucleus to induce LAMA4 transcription, providing a permissive signal for T-cell diapedesis.