Hypoxia also promotes EMT in HNSCC by NOTCH signaling activation117 and by regulating the metadherin (MTDH) loop.118 Through cooperative regulation of Twist and Bmi1, hypoxia represses E-cadherin, and p16INK4a expression to promote EMT in HNSCC.119 Interestingly, by increasing the expression of Twist, and reducing that of cyclin D1 and p16INK4, EMT promotes dormancy of disseminated tumor cells (DTCs) within the niche. This evidence concerns the gene MTDH and head and neck squamous cell carcinoma.