IL-1β Promotes Stemness of Tumor Cells by Activating Smad/ID1 Signaling Pathway
IL-1β Promotes Stemness of Tumor Cells by Activating Smad/ID1 Signaling Pathway
复制标题
IL-1β通过激活Smad/ID1信号通路促进肿瘤细胞的干细胞性
DOI：
10.7150/ijms.44285
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发表时间：
2020-01-01
影响因子：
3.6
通讯作者：
Liu, Guolong
中科院分区：
文献类型：
--
作者：
Lu, Lin;Wang, Peipei;Liu, Guolong
背景：据报道，IL-1 β参与了癌症的发展和远处转移。然而，IL-1 β在恶性行为中的潜在机制在很大程度上仍然未知。在本研究中，我们旨在研究IL-1 β是否可以增强肿瘤细胞的干性特性。方法：采用ELISA法检测头颈部鳞状细胞癌（HNSCC）和黑色素瘤患者血清IL-1 β的浓度。以HNSCC细胞SCC7和黑色素瘤细胞B16-F10为研究对象，研究IL-1 β对肿瘤细胞生长、迁移、侵袭及干细胞特性的影响及机制。进一步探讨了其潜在机制。结果：在HNSCC和黑色素瘤患者中，IL-1 β浓度的升高与肿瘤分期呈正相关。IL-1 β治疗导致体外和体内肿瘤生长显著增加。IL-1 β刺激促进细胞增殖、集落形成和致瘤性。此外，IL-1 β刺激的肿瘤细胞获得了增强的损伤愈合能力和侵袭能力。此外，IL-1 β刺激促进HNSCC细胞和黑色素瘤细胞的干细胞样能力，包括醛脱氢酶（+）（ALDH(+)）细胞的富集，干细胞相关标记物Nanog、OCT4和SOX2的上调，球体形成和化疗耐药。从机制上讲，IL-1 β处理促进了Smad1/5/8的磷酸化，并激活了其下游目标分化抑制剂1 （ID1）。沉默ID1可消除IL-1 β刺激诱导的球型形成，并上调干性基因的表达。结论：我们的数据表明IL-1 β通过激活Smad/ID1信号通路促进HNSCC和黑色素瘤细胞的干性。
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.