IL-1β Promotes Esophageal Squamous Cell Carcinoma Growth and Metastasis Through FOXO3A by Activating the PI3K/AKT Pathway

Esophageal cancer is a common type of cancer that poses a significant threat to human health. While the pro-inflammatory cytokine IL-1β has been known to contribute to the development of various types of tumors, its role in regulating esophageal cancer progression has not been extensively studied. Our studies found that the expression of IL-1β and FOXO3A was increased in esophageal squamous cell carcinoma (ESCC). IL-1β not only increased the proliferation, migration, and invasion of two ESCC cell lines but also promoted tumor growth and metastasis in nude mice. We also observed that IL-1β and FOXO3A regulated the process of epithelial-mesenchymal transition (EMT) and autophagy. The PI3K/AKT pathway was found to be involved in the changes of FOXO3A with the expression level of IL-1β. The AKT agonist (SC79) reversed the reduction of FOXO3A expression caused by the knockdown of IL-1β, indicating that IL-1β plays a role through the PI3K/AKT/FOXO3A pathway. Furthermore, the knockdown of FOXO3A inhibited ESCC development and attenuated the pro-cancer effect of overexpressed IL-1β. Targeting IL-1β and FOXO3A may be potentially valuable for the diagnosis and treatment of ESCC.