期刊
AUTOPHAGY
卷 18, 期 5, 页码 971-989出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1965421
关键词
Autophagy; lung metastasis; neutrophils; NFKB; particulate matter; ROS; TRAF6; TRIM37
类别
资金
- National Natural Science Foundation of China [81470212]
- Key Science Project of Zhejiang Province [WKJ-ZJ-2122]
- National Institute Of Environmental Health Sciences of the National Institutes of Health [P42ES013648]
Exposure to particulate matter is associated with increased incidence of lung cancer and metastasis, with neutrophil recruitment playing a central role in promoting lung cancer metastasis. The study highlights the coordination between lung epithelial cells and neutrophils in promoting cancer metastasis in response to PM exposure.
Epidemiological and clinical studies have shown that exposure to particulate matter (PM) is associated with an increased incidence of lung cancer and metastasis. However, the underlying mechanism remains unclear. Here, we demonstrated the central role of PM-induced neutrophil recruitment in promoting lung cancer metastasis. We found that reactive oxygen species (ROS)-mediated alveolar epithelial macroautophagy/autophagy was essential for initiating neutrophil chemotaxis and pre-metastatic niche formation in the lungs in response to PM exposure. During PM-induced autophagy, the E3 ubiquitin ligase TRIM37 was degraded and protected TRAF6 from proteasomal degradation in lung epithelial cells, which promoted the NFKB-dependent production of chemokines to recruit neutrophils. Importantly, ROS blockade, autophagy inhibition or TRAF6 knockdown abolished PM-induced neutrophil recruitment and lung metastasis enhancement. Our study indicates that host lung epithelial cells and neutrophils coordinate to promote cancer metastasis to the lungs in response to PM exposure and provides ideal therapeutic targets for metastatic progression.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据