CSCs are also capable of driving VM formation under stress conditions such as acidification and hypoxia in the tumor microenvironment by up-regulating the expression of the EMT transcription factors ZEB1/2, Snail, and Twist, and inhibiting E-cadherin, while promoting the expression of VE-cadherin, Fibronectin, and Vitronectin (Murai and Matsuda, 2023). This evidence concerns the gene TWIST1 and neoplasm.