Work

IL-1β Promotes Stemness of Tumor Cells by Activating Smad/ID1 Signaling Pathway

Year: 2020

Type: article

Abstract: Background: IL-1β is reported to be involved in cancer development and distant metastasis.However, the underlying mechanism of IL-1β upon malignant behaviors remains largely unknown.In this study, we aimed to study whether IL-1β could enhance the stemness traits of tumor cells. Methods:The concentrations of serum IL-1β in head and neck squamous cell carcinoma (HNSCC) and melanoma patients were detected using ELISA assay.The effect and mechanisms of IL-1β 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-1β were positively correlated with advanced tumor stage in both HNSCC and melanoma patients.IL-1β treatment led to a significant increase in tumor growth both in vitro and in vivo.IL-1β stimulation promoted cell proliferation, colony formation and tumorigenicity.In addition, IL-1β-stimulated tumor cells gained enhanced capabilities on wounding healing and invasion capabilities.Moreover, IL-1β 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-1β 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-1β stimulation.Conclusion: Our data demonstrates that IL-1β promotes the stemness of HNSCC and melanoma cells through activating Smad/ID1 signal pathway.

Source: International Journal of Medical Sciences

DOI: 10.7150/ijms.44285