Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway.
Cathelicidin, an antimicrobial peptide produced by macrophages, promotes colon cancer by activating the Wnt/β-catenin pathway.
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Cathelicidin 是一种由巨噬细胞产生的抗菌肽，通过激活 Wnt/β-catenin 通路促进结肠癌
DOI：
10.18632/oncotarget.2845
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发表时间：
2015-02-20
期刊：
影响因子：
--
通讯作者：
Wan H
中科院分区：
文献类型：
--
作者：
Li D;Liu W;Wang X;Wu J;Quan W;Yao Y;Bals R;Ji S;Wu K;Guo J;Wan H
在这里，我们发现，与非癌组织相比，结肠癌组织中抗菌肽cathelicidin的水平有所增加。重要的是，cathelicidin主要在免疫细胞中表达。与肿瘤细胞接触导致巨噬细胞分泌凯萨林菌素。在体内，cathelicidin的中和作用显著降低了巨噬细胞向结肠肿瘤中的植入以及肿瘤细胞的增殖，导致肿瘤生长的抑制。此外，用凯萨林菌素中和抗体处理在体内和体外都使肿瘤细胞中的Wnt/β-连环蛋白信号传导途径失活。Cathelicidin通过诱导PTEN磷酸化激活Wnt/β-catenin信号，导致PI 3 K/Akt信号激活和随后的GSK 3 β磷酸化，导致β-catenin的稳定和核转位。这些数据表明，由肿瘤微环境中的免疫细胞表达的cathelicidin通过激活PTEN/PI 3 K/Akt和Wnt/β-连环蛋白信号通路促进结肠癌生长。
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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