Transforming growth factor-β signaling in head and neck squamous cell carcinoma: Insights into cellular responses.

Head and neck squamous cell carcinoma (HNSCC) arises in the oral cavity, salivary glands, larynx, pharynx, nasal cavity and paranasal sinuses, and is characterized by high morbidity and metastasis rates. Transforming growth factor-β (TGF-β) is a homodimeric protein known to be a multifunctional regulator in target cells and to serve a pivotal role in numerous types of cancer, including HNSCC. The role of TGF-β signaling in carcinogenesis can change from tumor-suppressing to tumor-promoting. In addition, TGF-β induces epithelial-mesenchymal transition and restrains immune surveillance on malignant cells. In the present review, the effects of TGF-β signaling at a cellular level were discussed, which includes the regulation of tumor cells, immune cells and other stromal cells, as well as the possible mechanisms underlying the conversion from a tumor suppressor to a tumor promoter in HNSCC. Further research is required to improve the understanding on how this network is involved in carcinogenesis, progression and metastases in HNSCC.