Additionally, IL-6 secreted by tumor and many stromal cells through upregulation of Snail via the STAT3 pathway, and stabilizing Twist via casein kinase 2 (CK2) promote HNSCC EMT.116 Hypoxia is the vital component of TME and a vital contributor to metastasis and has been shown to induce EMT. This evidence concerns the gene STAT3 and head and neck squamous cell carcinoma.