TGF-β1 activates EMT in HNSCC through a SMAD-dependent pathway [51,55,56,57,58] and is instrumental in the formation of tumor buds that detach from primary tumors in oral SCC (OSCC) via activation of ZEB1 and paired-related homeobox 1 protein PRRX1 [59]. This evidence concerns the gene PRRX1 and head and neck squamous cell carcinoma.