Transforming Growth Factor Beta (TGF-β) Signaling in Head and Neck Squamous Cell Carcinoma (HNSCC)

Abstract

Transforming growth factor receptor beta (TGF-β) signaling is commonly dysregulated in head and neck squamous cell carcinoma (HNSCC). TGF-β signaling influences homeostasis in normal epithelial cells and regulates a critical signaling network during development. In HNSCC, TGF-β signaling frequently promotes cell invasion, metastasis, proliferation, and drug resistance and may present an important therapeutic target. Canonical TGF-β signaling generally involves activation of SMAD effector proteins, most prominently SMAD2 and SMAD3, whereas noncanonical TGF-β signaling requires signal propagators including ERK, AKT, and RAF, also commonly employed by receptor tyrosine kinases (RTKs), thereby providing opportunities for signaling crosstalk. Several members of the TGF-β superfamily are being explored as potential targets to control drug resistance and metastatic spread, both important barriers to cure in HNSCC. In this chapter, the roles of TGF-β in HNSCC are described, with particular focus on molecular signaling, TGF-β’s role in controlling gene expression, and relevant therapeutic directions involving TGF-β.