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

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.

NSE, positively regulated by LINC00657-miR-93-5p axis, promotes small cell lung cancer (SCLC) invasion and epithelial-mesenchymal transition (EMT) process

“…Firstly, total RNA was extracted from tissue specimens and cell lines using TRIzol reagent as previously described 20 , 21 . Then complementary DNA was synthesized based on reverse transcription from total RNA using Takara cDNA Synthesis Kit.…”

“…Total proteins from tissues specimens and cell lines were extracted using RIPA solution as previously described 20 , 21 . Briefly, total proteins were separated using SDS-PAGE and transferred to PVDF membrane.…”

The Role of Immune Modulatory Cytokines in the Tumor Microenvironments of Head and Neck Squamous Cell Carcinomas

“…Investigations of salivary transcriptomic and proteomic biomarkers have shown that the concentration of IL-1β in combination with IL-8 was notably higher in OSCC patients compared to that in dysplasia patients [ 35 ]. As a result of its interaction with the activation of the Smad/ID1 signal pathway, IL-1β promotes the stemness, cancer development, and distant metastasis of HNSCCs [ 36 ]. IL-1β modulates Snail, which in turn causes the downregulation of E-cadherin and the upregulation of COX-2, resulting in the promotion of the EMT in HNSCCs under inflammatory conditions [ 37 ].…”

Roles of IL-1 in Cancer: From Tumor Progression to Resistance to Targeted Therapies

“…The ability of cancer cells to acquire a stem-like phenotype is a hallmark in tumors. Studies of molecular mechanisms have shown that IL-1β promotes the stemness of HNSCC and melanoma cells, through the activation of Smad/ID1 signalling pathways and the upregulation of stemness factor genes (Bmi1 and Nestin), thus increasing drug resistance [ 29 , 77 ]. This phenotype is critically associated with tumor progression and therapy failure.…”