CCDC25: precise navigator for neutrophil extracellular traps on the prometastatic road

摘要

The dissemination of cancer cells called metastasis accounts forthe majority of deaths of cancer patients. Neutrophil extracellulartraps (NETs) released by neutrophils to fight pathogens have beenshown to promote metastasis in mouse models. However, themechanism behind how NETs boost metastasis remains elusive. Ina recent study in Nature,1 Yang et al reported that NETs areabundant in the liver metastases of patients with breast and coloncancers, and that the risk of liver metastasis in patients with earlystagebreast cancer can be predicted by monitoring the levels ofserum NETs. Furthermore, Yang et al.1 elucidated that the DNAcomponent of NETs (NET-DNA) acts as a chemotactic factor that isrecognized by coiled-coil domain containing protein 25 (CCDC25),a cytoplasmic membrane-localized extracellular DNA sensor ofcancer cells, which in turn activates the integrin-linked kinase(ILK)–β-parvin–RAC1–CDC42 cascade to promote metastasis (Fig.1). The clinical importance of CCDC25 was confirmed by Yanget al.,1 and targeting CCDC25 inhibits NET-mediated metastasis inmouse models, suggesting a potential therapeutic strategy to haltthe metastasis.