血小板
线粒体
氧化磷酸化
血小板活化
细胞生物学
癌症研究
磷酸化
转移
生物
化学
免疫学
癌症
生物化学
遗传学
作者
Zilong Zhang,Xu Xu,Di Zhang,Songsong Zhao,Chuyi Wang,Guilin Zhang,Wenshu Chen,Jinglin Liu,Huimin Gong,Youlutuziayi Rixiati,Li Shi,Tong Shen,Jian‐Ming Li
出处
期刊:Cell Metabolism
[Elsevier]
日期:2024-03-01
卷期号:36 (3): 541-556.e9
被引量:2
标识
DOI:10.1016/j.cmet.2023.12.020
摘要
Summary
The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient platelets have increasing mitochondrial oxidative phosphorylation and secrete lipid metabolites like acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM. Notably, Acar enhanced the activity of mitochondrial electron transport chain complex and mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically. Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lung metastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppresses B cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.
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