Research Papers:

Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway

Dong Li _, Wenfan Liu, Xuan Wang, Junlu Wu, Wenqiang Quan, Yiwen Yao, Robert Bals, Shurong Ji, Kaiyin Wu, Jia Guo and Haiying Wan

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Oncotarget. 2015; 6:2939-2950. https://doi.org/10.18632/oncotarget.2845

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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

Correspondence to:

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.

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