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宋尔卫/苏士成团队发现中性粒细胞胞外陷阱促进肿瘤转移机制
2020-06-12 14:07
来源：小柯机器人

中山大学宋尔卫、苏士成等研究人员合作发现，中性粒细胞胞外陷阱（NET）中的DNA通过CCDC25促进癌症转移。2020年6月11日，《自然》在线发表了这一成果。

研究人员发现NET在乳腺癌和结肠癌患者的肝转移中富集，而血清NET可以预测早期乳腺癌患者肝转移的发生。NET-DNA充当吸引癌细胞的趋化因子，而不仅仅是充当癌细胞的“陷阱”。在几种小鼠模型中，研究人员发现肝脏或肺中的NET吸引癌细胞形成远处转移。
 
研究人员将跨膜蛋白CCDC25鉴定为癌细胞上的NET-DNA受体，该受体可感知细胞外DNA，并随后激活ILK-β-parvin途径来增强细胞移动。NET介导的转移在CCDC25基因敲除细胞中被阻碍。临床上，研究人员发现CCDC25在原发性癌细胞上的表达与患者预后差有关。
 
总体而言，研究人员报道了调控NET依赖性转移的跨膜DNA受体，并认为靶向CCDC25可能是预防癌症转移的潜在治疗策略。
 
据介绍，NET由嗜中性粒细胞释放用于捕获微生物，其包含被颗粒蛋白包裹的染色质DNA。最近的研究表明，NET的DNA成分（NET-DNA）与小鼠模型中的癌症转移有关。但是，尚不清楚NET-DNA在癌症患者转移中的功能作用和临床重要性。
 
附：英文原文

Title: DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25

Author: 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

Issue&Volume: 2020-06-11

Abstract: Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1,2,3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4,5,6. 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.

DOI: 10.1038/s41586-020-2394-6

Source: https://www.nature.com/articles/s41586-020-2394-6

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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