Details

Autor(en) / Beteiligte

• Yang, Linbin
• Liu, Qiang
• Zhang, Xiaoqian
• Liu, Xinwei
• Zhou, Boxuan
• Chen, Jianing
• Huang, Di
• Li, Jiaqian
• Li, Heliang
• Chen, Fei
• Liu, Jiang
• Xing, Yue
• Chen, Xueman
• Su, Shicheng
• Song, Erwei

Titel

DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25

Ist Teil von

• Nature (London), 2020-07, Vol.583 (7814), p.133-138

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms 1 – 3 . Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models 4 – 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. DNA from neutrophil extracellular traps interacts with the transmembrane receptor CCDC25 on cancer cells, activating the ILK-β-parvin pathway to enhance cell motility and promote distant metastases.