结直肠癌
医学
淋巴管新生
癌症研究
转移
成纤维细胞活化蛋白
淋巴系统
淋巴结
淋巴
癌细胞
上皮-间质转换
癌症
肿瘤科
内科学
病理
作者
Shuran Fan,Ming Qi,Qi Qi,Qun Miao,Lijuan Deng,Jinghua Pan,Shenghui Qiu,Jiashuai He,Maohua Huang,Xiaobo Li,Jie Huang,Jianghai Lin,Wen-Yu Lyu,Weiqing Deng,Yanan He,Xuesong Liu,Lvfen Gao,Dongmei Zhang,Wen‐Cai Ye,Minfeng Chen
标识
DOI:10.1016/j.apsb.2023.11.002
摘要
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
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