IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation

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Show simple item record Li, Yijing Wang, Lei Pappan, Loretta Galliher-Beckley, Amy Shi, Jishu N. 2013-03-20T14:59:14Z 2013-03-20T14:59:14Z 2013-03-20
dc.description.abstract Background: IL-1β is a pleiotropic pro-inflammatory cytokine and its up-regulation is closely associated with various cancers including gastrointestinal tumors. However, it remains unclear how IL-1β may contribute to the initiation and development of these inflammation-associated cancers. Here we investigated the role of IL-1β in colon cancer stem cell (CSC) development. Methods: Using self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis, immunoblot assay and shRNA knockdown, we determined the effects of IL-1β on cancer stem cell development and epithelial-mesenchymal transition (EMT) in human primary colon cancer cells and colon cancer cell line HCT-116. Results: We found that IL-1β can increase sphere-forming capability of colon cancer cells in serum-free medium. IL-1β-induced spheres displayed an up-regulation of stemness factor genes (Bmi1 and Nestin) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1β-induced spheres, indicating that there might be a close association between EMT and IL-1β-induced CSC self-renewal. Indeed, IL-1β treatment led to EMT of colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT-116 cells reversed IL-1β-induced EMT and stem cell formation. Conclusion: Our findings indicate that IL-1β may promote colon tumor growth and invasion through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in these two processes. Thus, IL-1β and Zeb1 might be new therapeutic targets against colon cancer stem cells. en_US
dc.language.iso en_US en_US
dc.relation.uri en_US
dc.subject Colon cancer en_US
dc.subject Tumor microenvironment en_US
dc.subject Inflammation en_US
dc.subject Interleukin-1β en_US
dc.subject Cancer stem cells en_US
dc.subject Epithelialmesenchymal transition en_US
dc.subject Zeb1 en_US
dc.title IL-1β promotes stemness and invasiveness of colon cancer cells through Zeb1 activation en_US
dc.type Article (publisher version) en_US 2012 en_US
dc.citation.doi doi:10.1186/1476-4598-11-87 en_US
dc.citation.jtitle Molecular Cancer en_US
dc.citation.spage 87 en_US
dc.citation.volume 11 en_US
dc.contributor.authoreid leiwang en_US
dc.contributor.authoreid jshi en_US

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