Il-1 Beta Promotes Stemness Of Tumor Cells By Activating Smad/Id1 Signaling Pathway

Background: IL-1 beta is reported to be involved in cancer development and distant metastasis. However, the underlying mechanism of IL-1 beta upon malignant behaviors remains largely unknown. In this study, we aimed to study whether IL-1 beta could enhance the stemness traits of tumor cells.Methods: The concentrations of serum IL-1 beta in head and neck squamous cell carcinoma (HNSCC) and melanoma patients were detected using ELISA assay. The effect and mechanisms of IL-1 beta on tumor cell growth, migration, invasion and stemness characters were studied using HNSCC cell SCC7 and melanoma cell B16-F10. The underlying mechanisms were further explored.Results: Enhanced concentrations of IL-1 beta were positively correlated with advanced tumor stage in both HNSCC and melanoma patients. IL-1 beta treatment led to a significant increase in tumor growth both in vitro and in vivo. IL-1 beta stimulation promoted cell proliferation, colony formation and tumorigenicity. In addition, IL-1 beta-stimulated tumor cells gained enhanced capabilities on wounding healing and invasion capabilities. Moreover, IL-1 beta stimulation promoted the stem-like capabilities of both HNSCC cells and melanoma cells, including the enrichment of aldehyde dehydrogenase(+) (ALDH(+)) cells, up-regulation of stem cell related markers Nanog, OCT4, and SOX2, sphere formation and chemoresistance. Mechanistically, IL-1 beta treatment promoted the phosphorylation of Smad1/5/8 and activated its downstream target inhibitor of differentiation 1 (ID1). Silencing ID1 abrogated sphere formation and upregulated expression of stemness genes which were induced by IL-1 beta stimulation.Conclusion: Our data demonstrates that IL-1 beta promotes the stemness of HNSCC and melanoma cells through activating Smad/ID1 signal pathway.