Transforming growth factor β1 enhances sternness of head and neck squamous cell carcinoma cells through activation of Wnt signaling

Transforming growth factor beta (TGF beta) ligands, including TGF beta 1, are multifunctional cytokines known as key regulators of cell growth, differentiation and inflammation. Dysregulated TGF beta signaling is common in numerous solid tumors, including head and neck squamous cell carcinoma (HNSCC). Previously, TGF beta ligands were also reported to be associated with an enhancement of sternness in glioma stem-like cells. However, their role in HNSCC cancer stem cells (CSCs) has not been explored. The present study demonstrated that TGF beta 1 enriches the properties of HNSCC CSCs. TGF beta 1 promoted sphere formation and increased sternness-associated gene expression (Oct4 and Sox2) of primary HNSCC CSCs. Additionally, the population of aldehyde dehydrogenase (ALDH)-positive cells was increased subsequent to exogenous treatment of cells with TGF beta 1. In addition, following stimulation with TGF beta 1, the cells exhibited more resistance to cisplatin and elevated expression of Twist, Snail and Slug. Mechanistically, TGF beta 1 acts as an upstream stimulator of Wnt/beta-catenin signaling. Collectively, the present findings provide insights toward the development of TGF beta 1 signaling inhibition strategies for treating HNSCC CSCs.