title: Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway.
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.
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of General Surgery, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Putuo People's Hospital, 200060 Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Junlu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Quan
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Internal Medicine V - Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University Hospital, 66424 Homburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of General Surgery, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Shurong
authors.initials: S
authors.lastname: Ji
authors.affiliation: Institute of Pathology, Charité University Hospital, 12200 Berlin, Germany.
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.affiliation: Tongji University Suzhou Institute, 215000 Suzhou, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Tongji Hospital of Tongji University, 200065 Shanghai, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Wan
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D018920:Coculture Techniques; D003092:Colitis / Q000150:complications* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D045325:HCT116 Cells; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D059016:Tumor Microenvironment; D020298:U937 Cells; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism*; D054804:Cathelicidins
chemical_list: D057134:Antibodies, Neutralizing; D023181:Antimicrobial Cationic Peptides; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D058539:Phosphatidylinositol 3-Kinase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D054804:Cathelicidins