Head and neck squamous cell carcinoma (HNSCC) is the most common cancer in the head and neck region. Despite advances in surgery and chemotherapy, HNSCC has the lowest five-year survival rate among major cancers. TGFβ is a multifunctional cytokine. TGFβ suppresses tumor formation. Paradoxically, it also promotes cancer metastasis. We are using conditional transgenic/knockout mouse models to alter individual TGFb1 signaling components in head and neck epithelia and skin epidermis, in order to determine the mechanisms of TGFβ effects on cancer, including TGFβ signaling through pathways of Smad, MAPK, Rho, etc.