Cancer- associated fibroblast- derived SEMA3C facilitates colorectal cancer liver metastasis via NRP2-mediated MAPK activation

• 成果类型: Article
• 署名作者: Zhang, Yuyuan; Zuo, Anning; Ba, Yuhao; Liu, Shutong; Chen, Jingqi; Yang, Shuaixi; Weng, Siyuan; Chen, Yukang; Xu, Hui; Luo, Peng; Cheng, Quan; Tang, Bufu; Liu, Benyu; Zhang, Chuhan; Yang, Jingkuan; Han, Xinwei; Liu, Zaoqu
• 署名单位: Zhengzhou University; Zhengzhou University; Zhengzhou University; Zhengzhou University; Southern Medical University - China; Central South University; Fudan University; Zhengzhou University; Zhengzhou University; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11020
• DOI: 10.1073/pnas.2423077122
• 发表日期: 2025-05-22
• 关键词: microenvironment; landscape; pathways; DYNAMICS; subtypes; GROWTH

摘要

Liver metastasis remains the predominant cause of mortality in patients with colorectal cancer (CRC). Nevertheless, the mechanisms underlying the initiation of colorectal cancer liver metastasis remain poorly elucidated. During the metastatic process of CRC cells from the primary site to the liver, we performed time- resolved analyses and identified a subset of tumor cells spatially located in the primary tumor and temporally distributed in the early stages of liver metastasis. These cells were termed liver active interaction with surrounding stromal components, and a close association with liver metastasis. Notably, we found significant interactions between cancer- associated in vivo and in vitro experiments confirmed that CAF- secreted SEMA3C could bind to cer liver metastasis. Our findings suggest potential therapeutic strategies for the early prevention of colorectal cancer liver metastasis.