SMAD4 and head and neck squamous cell carcinoma: Since SMAD4 mutations are associated with a mesenchymal phenotype, invasion, and metastasis [19] and the UM-SCC-22B cell line exhibited such a phenotype, it was obvious to assume that the SMAD4 mutation observed in UM-SCC-22B is functionally related to the phenotype of this HNSCC cell line.