补语(音乐)
糖基化
补体系统
凝结
化学
癌症研究
转移
细胞生物学
医学
免疫学
生物化学
生物
癌症
内科学
抗体
基因
互补
表型
作者
Xinyu Chen,Wei Bao,Kaiyuan Liu,Na Jing,Genyu Du,Luyao Jiang,Qian You,Yingchao Zhang,Penghui Xu,Chaping Cheng,Nan Wang,Xialian Xi,Mingyue Wang,Yiyun Liu,Jinming Wang,Huifang Zhao,Shilei Zhang,Dinglan Wu,Chi‐Fai Ng,Jiahua Pan
标识
DOI:10.1002/advs.202504809
摘要
Abstract Liver metastasis is prevalent among patients with neuroendocrine prostate cancer (NEPC) and other types of neuroendocrine (NE) cancers, featuring with an aggressive clinical course and a dismal prognosis. However, the cellular and molecular mechanisms underlying liver‐specific metastatic tropism in NE cancers remain poorly understood. Intriguingly, it is found that NEPC liver metastatic foci are frequently associated with thrombi. NEPC cells express an aberrantly elevated level of glycosyltransferase Galnt9. Notably, the Galnt9‐mediated O‐GalNAc glycosylation on the cell membrane of NE cancer cells, particularly on the adhesion molecule Annexin A2, activates the mannose‐binding lectin (MBL) complement signaling in the liver. This cascade stimulates platelet activation and thrombus formation, ultimately facilitating hepatic metastasis of NEPC. Inhibition of O‐GalNAc glycosylation or knockdown of Galnt9 demonstrates efficacy in restraining the liver metastasis of NEPC, small cell lung cancer (SCLC), and colorectal neuroendocrine cancer. These findings identify Galnt9‐mediated O‐GalNAc glycosylation as a targetable mechanism driving liver metastasis through activation of MBL complement and coagulation cascades across a broad spectrum of NE cancers.
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