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

Molecular Cancer

Research

Jishu Shi¹  Lei Wang¹  Yijing Li¹  Loretta Pappan¹  Amy Galliher-Beckley¹ 

[1] Department of Anatomy and Physiology, College of Veterinary Medicine, 66506, Manhattan, KS, USA;

关键词: Colon cancer;    Tumor microenvironment;    Inflammation;    Interleukin-1β;    Cancer stem cells;    Epithelial-mesenchymal transition;    Zeb1;   

DOI  :  10.1186/1476-4598-11-87

 received in 2012-06-01, accepted in 2012-11-05,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundIL-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.MethodsUsing 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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.