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Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

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资源类型：
Pubmed体系：

收录情况： ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越：领军期刊

作者：
Fan Shuran[1,2] * ; Qi Ming[1,2,3] * ; Qi Qi[4] * ; Miao Qun[1,2] ; Deng Lijuan[5] ; Pan Jinghua[3] ; Qiu Shenghui[3] ; He Jiashuai[3] ; Huang Maohua[1,2] ; Li Xiaobo[1,2] ; Huang Jie[1,2] ; Lin Jiapeng[2] ; Lyu Wenyu[2] ; Deng Weiqing[2] ; He Yingyin[2] ; Liu Xuesong[3] ; Gao Lvfen[3] ; Zhang Dongmei[1,2] ; Ye Wencai[1,2] ; Chen Minfeng[1,2,6] ;
机构： [1]State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China. [2]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. [3]The First Affiliated Hospital of Jinan University, Guangzhou 510632, China. [4]School of Medicine, Jinan University, Guangzhou 510632, China. [5]School of Traditional Chinese Medicine, Jinan University, Guangzhou 510630, China. [6]State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China.
出处：
DOI： 10.1016/j.apsb.2023.11.002
ISSN：

关键词： Lymphatic metastasis Colorectal cancer Fibroblast activation protein a FAPa-activated prodrug Epithelialemesenchymal

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.© 2024 The Authors.

基金：
National Natural Science Foundation of China (82273941, 81973340, 82204427, 81803566, 82003796, 81773758), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01Y036, China), Natural Science Foundation of Guangdong Province (2022A1 515011813, 2021A1515110242, 2020A1515010071, 2019A15 15010144, 2019A1515110543, 2019A1515011934, China),Ministry of Science and Technology of China (2018ZX09711001-008-008), National high-level personnel of special support program (Zhang Dongmei), National Key R&D Program of China (2017YFC 1703800), Technology Key Project of Guangdong Province (2020B1111110004, China), Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy (2020B1212060076, China), Special Funds for the Cultivation of Guangdong College Students’ Scientifc and Technological Innovation (“Climbing Program” Special Funds) (pdjh2021a0052, China), Science and Technology Projects in Guangzhou (2023A03J0602, 202201010173, 202102070001, 202002030010, China), Young S&T Talent Training Program of Guangdong Provincial Association for S&T, China (SKXRC202216), Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University (JNU1AF-CFTP-2022- a01227, China), China Postdoctoral Science Foundation (2022M 711345, China).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 1 区 药学
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 药学
第一作者：
第一作者机构： [1]State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China. [2]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China. [2]Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China. [6]State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China.
推荐引用方式(GB/T 7714)：
Fan Shuran,Qi Ming,Qi Qi,et al.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis[J].Acta Pharmaceutica Sinica B.2024,14(2):682-697.doi:10.1016/j.apsb.2023.11.002.
APA：
Fan Shuran,Qi Ming,Qi Qi,Miao Qun,Deng Lijuan...&Chen Minfeng.(2024).Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.Acta Pharmaceutica Sinica B,14,(2)
MLA：
Fan Shuran,et al."Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis".Acta Pharmaceutica Sinica B 14..2(2024):682-697

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