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.
Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway
Dong Li,Wenfang Liu,Xuan Wang,Junlu Wu,W. Quan,Yiwen Yao,R. Bals,Shu-rong Ji,Kaiyin Wu,Jia Guo,Hai-ying Wan
Published 2014 in OncoTarget
ABSTRACT
PUBLICATION RECORD
- Publication year
2014
- Venue
OncoTarget
- Publication date
2014-12-15
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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