Hypoxia in the tumor environment activates various signaling pathways (e.g., HIF, c-Myc, Sox-2, Oct-4, adenosine/STAT3/IL-6 pathway, MAPK/ERK pathway, Notch, Wnt, Hedgehog, and Hippo signaling) [234], promoting the multi-directional differentiation potential of CSCs and influencing CSC transformation into incomplete endothelial cells that exhibit VM in different tumor types (e.g., oral squamous cell carcinoma, breast cancer, liver cancer, colorectal cancer, and cholangiocarcinoma) [235–239]. This evidence concerns the gene SOX2 and neoplasm.