Cathelicidin, an Antimicrobial Peptide Produced by Macrophages, Promotes Colon Cancer by Activating the Wnt/β-catenin Pathway

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Jan 19

PMID 25596747

Citations 12

Authors

Dong Li

Wenfang Liu

Xuan Wang

Junlu Wu

Wenqiang Quan

Yiwen Yao

Robert Bals

Shurong Ji

Kaiyin Wu

Jia Guo

Haiying Wan

Affiliations

Soon will be listed here.

Abstract

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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