Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway
Metrics: PDF 2706 views | HTML 2654 views | ?
Dong Li1,*, Wenfang Liu2,*, Xuan Wang3, Junlu Wu1, Wenqiang Quan1, Yiwen Yao1, Robert Bals4, Shurong Ji2, Kaiyin Wu5, Jia Guo6, Haiying Wan1
1Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China
2Department of General Surgery, Tongji Hospital of Tongji University, 200065 Shanghai, China
3Department of Pharmacy, Putuo People’s Hospital, 200060 Shanghai, China
4Department of Internal Medicine V – Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany
5Institute of Pathology, Charité University Hospital, 12200 Berlin, Germany
6Tongji University Suzhou Institute, 215000 Suzhou, China
*These authors have contributed equally to this work
Dong Li, e-mail: [email protected]
Keywords: Cathelicidin, Colon cancer, Macrophage, Wnt/β-catenin, Growth
Received: June 27, 2014 Accepted: December 03, 2014 Published: December 15, 2014
Here we found that levels of cathelicidin, an antimicrobial peptide, were increased in colon cancer tissues compared to noncancerous tissues. Importantly, cathelicidin was mainly expressed in immune cells. Contact with tumor cells caused macrophages to secrete cathelicidin. Neutralization of cathelicidin, in vivo, significantly reduced the engraftment of macrophages into colon tumors, as well as proliferation of tumor cells, resulting in an inhibition of tumor growth. Furthermore, treatment with cathelicidin neutralizing antibody de-activated the Wnt/β-catenin signaling pathway in tumor cells both in vivo and in vitro. Cathelicidin activated Wnt/β-catenin signaling by inducing phosphorylation of PTEN, leading to activation of PI3K/Akt signaling and subsequent phosphorylation of GSK3β, resulting in stabilization and nuclear translocation of β-catenin. These data indicate that cathelicidin, expressed by immune cells in the tumor microenvironment, promotes colon cancer growth through activation of the PTEN/PI3K/Akt and Wnt/β-catenin signaling pathways.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.