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DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25

Author

Listed:
  • Linbin Yang

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Qiang Liu

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Xiaoqian Zhang

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Xinwei Liu

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Boxuan Zhou

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jianing Chen

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Di Huang

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jiaqian Li

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Heliang Li

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Fei Chen

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Jiang Liu

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Yue Xing

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Xueman Chen

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Shicheng Su

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Erwei Song

    (Sun Yat-Sen University
    Sun Yat-Sen University
    Sun Yat-Sen University
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory)

Abstract

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1–3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4–6. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear. Here we show that NETs are abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs can predict the occurrence of liver metastases in patients with early-stage breast cancer. NET-DNA acts as a chemotactic factor to attract cancer cells, rather than merely acting as a ‘trap’ for them; in several mouse models, NETs in the liver or lungs were found to attract cancer cells to form distant metastases. We identify the transmembrane protein CCDC25 as a NET-DNA receptor on cancer cells that senses extracellular DNA and subsequently activates the ILK–β-parvin pathway to enhance cell motility. NET-mediated metastasis is abrogated in CCDC25-knockout cells. Clinically, we show that the expression of CCDC25 on primary cancer cells is closely associated with a poor prognosis for patients. Overall, we describe a transmembrane DNA receptor that mediates NET-dependent metastasis, and suggest that targeting CCDC25 could be an appealing therapeutic strategy for the prevention of cancer metastasis.

Suggested Citation

  • Linbin Yang & Qiang Liu & Xiaoqian Zhang & Xinwei Liu & Boxuan Zhou & Jianing Chen & Di Huang & Jiaqian Li & Heliang Li & Fei Chen & Jiang Liu & Yue Xing & Xueman Chen & Shicheng Su & Erwei Song, 2020. "DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25," Nature, Nature, vol. 583(7814), pages 133-138, July.
  • Handle: RePEc:nat:nature:v:583:y:2020:i:7814:d:10.1038_s41586-020-2394-6
    DOI: 10.1038/s41586-020-2394-6
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    Cited by:

    1. Weiwei Dai & Ruotong Tian & Liubing Yu & Shasha Bian & Yuling Chen & Bowen Yin & Yuxuan Luan & Siqi Chen & Zhuoyang Fan & Rucheng Yan & Xin Pan & Yingyong Hou & Rong Li & Juxiang Chen & Minfeng Shu, 2024. "Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Zhiyuan Zheng & Ya-nan Li & Shanfen Jia & Mengting Zhu & Lijuan Cao & Min Tao & Jingting Jiang & Shenghua Zhan & Yongjing Chen & Ping-Jin Gao & Weiguo Hu & Ying Wang & Changshun Shao & Yufang Shi, 2021. "Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    3. Marianna Ioannou & Dennis Hoving & Iker Valle Aramburu & Mia I. Temkin & Nathalia M. Vasconcelos & Theodora-Dorita Tsourouktsoglou & Qian Wang & Stefan Boeing & Robert Goldstone & Spyros Vernardis & V, 2022. "Microbe capture by splenic macrophages triggers sepsis via T cell-death-dependent neutrophil lifespan shortening," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    4. Ting Wang & Yingli Zhou & Zilong Zhou & Pinggen Zhang & Ronghui Yan & Linchong Sun & Wenhao Ma & Tong Zhang & Shengqi Shen & Haiying Liu & Hui Lu & Ling Ye & Junru Feng & Zhaolin Chen & Xiuying Zhong , 2023. "Secreted protease PRSS35 suppresses hepatocellular carcinoma by disabling CXCL2-mediated neutrophil extracellular traps," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Junho Lee & Donggu Lee & Sean Lawler & Yangjin Kim, 2021. "Role of neutrophil extracellular traps in regulation of lung cancer invasion and metastasis: Structural insights from a computational model," PLOS Computational Biology, Public Library of Science, vol. 17(2), pages 1-29, February.
    6. Xiang Xia & Zizhen Zhang & Chunchao Zhu & Bo Ni & Shuchang Wang & Shuofei Yang & Fengrong Yu & Enhao Zhao & Qing Li & Gang Zhao, 2022. "Neutrophil extracellular traps promote metastasis in gastric cancer patients with postoperative abdominal infectious complications," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Weili Wang & Huizhen Zheng & Jun Jiang & Zhi Li & Dongpeng Jiang & Xiangru Shi & Hui Wang & Jie Jiang & Qianqian Xie & Meng Gao & Jianhong Chu & Xiaoming Cai & Tian Xia & Ruibin Li, 2022. "Engineering micro oxygen factories to slow tumour progression via hyperoxic microenvironments," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    8. Shu Zhang & Wen Fang & Siqi Zhou & Dongming Zhu & Ruidong Chen & Xin Gao & Zhuojin Li & Yao Fu & Yixuan Zhang & Fa Yang & Jing Zhao & Hao Wu & Pin Wang & Yonghua Shen & Shanshan Shen & Guifang Xu & Le, 2023. "Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. Lixia Chen & Peiling Dai & Lei Liu & Yujia Chen & Yanxia Lu & Lin Zheng & Haowei Wang & Qinzi Yuan & Xuenong Li, 2024. "The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    10. Raymond K. H. Yip & Joel S. Rimes & Bianca D. Capaldo & François Vaillant & Kellie A. Mouchemore & Bhupinder Pal & Yunshun Chen & Elliot Surgenor & Andrew J. Murphy & Robin L. Anderson & Gordon K. Smy, 2021. "Mammary tumour cells remodel the bone marrow vascular microenvironment to support metastasis," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    11. Guanqun Li & Liwei Liu & Tianqi Lu & Yuhang Sui & Can Zhang & Yongwei Wang & Tao Zhang & Yu Xie & Peng Xiao & Zhongjie Zhao & Chundong Cheng & Jisheng Hu & Hongze Chen & Dongbo Xue & Hua Chen & Gang W, 2023. "Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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