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Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/?-catenin signaling.

ABSTRACT: Rationale: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity. In addition, LL-37 is involved in the regulation of tumor cell growth. However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood. Methods: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistological, immunofluorescence analysis, and enzyme-linked immunosorbent assay. The animal model of wild-type and Cramp knockout mice was employed to evaluate the tumorigenic effect of LL-37 in non-small cell lung cancer. The mechanism of LL-37 involving in the promotion of lung tumor growth was evaluated via microarray analyses, recombinant protein treatment approaches in vitro, tumor immunohistochemical assays, and intervention studies in vivo. Results: LL-37 produced by myeloid cells was frequently upregulated in primary human lung cancer tissues. Moreover, its expression level correlated with poor clinical outcome. LL-37 activated Wnt/?-catenin signaling by inducing the phosphorylation of protein kinase B and subsequent phosphorylation of glycogen synthase kinase 3? mediated by the toll-like receptor-4 expressed in lung tumor cells. LL-37 treatment of tumor cells also decreased the levels of Axin2. In contrast, it elevated those of an RNA-binding protein (tristetraprolin), which may be involved in the mechanism through which LL-37 induces activation of Wnt/?-catenin. Conclusion: LL-37 may be a critical molecular link between tumor-supportive immune cells and tumors, facilitating the progression of lung cancer.

SUBMITTER: Ji P

PROVIDER: S-EPMC6531301 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling.

Ji Ping P Zhou Yongxin Y Yang Yibao Y Wu Junlu J Zhou Hao H Quan Wenqiang W Sun Junjun J Yao Yiwen Y Shang Anquan A Gu Chenzheng C Zeng Bingjie B Firrman Jenni J Xiao Weidong W Bals Robert R Sun Zujun Z Li Dong D

Theranostics 20190412 8

<b>Rationale</b>: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity. In addition, LL-37 is involved in the regulation of tumor cell growth. However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood. <b>Methods</b>: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistolo ...[more]

PMID: 31149039

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Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/?-catenin signaling.

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Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling.

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