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

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

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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.

Lymphatic metastasisColorectal cancerFibroblast activation protein αFAPα-activated prodrugEpithelial-mesenchymal transitionSTAT3Extracellular matrix remodelingImmunosuppressive

Shuran Fan、Ming Qi、Qi Qi、Qun Miao、Lijuan Deng、Jinghua Pan、Shenghui Qiu、Jiashuai He、Maohua Huang、Xiaobo Li、Jie Huang、Jiapeng Lin、Wenyu Lyu、Weiqing Deng、Yingyin He、Xuesong Liu、Lvfen Gao、Dongmei Zhang、Wencai Ye、Minfeng Chen

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State Key Laboratory of Bioactive Molecules and Druggability Assessment,Jinan University,Guangzhou 510632,China

buangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research,College of Pharmacy,Jinan University,Guangzhou 510632,China

The First Affiliated Hospital of Jinan University,Guangzhou 510632,China

School of Medicine,Jinan University,Guangzhou 510632,China

School of Traditional Chinese Medicine,Jinan University,Guangzhou 510630,China

State Key Laboratory of Chemical Oncogenomics,Guangdong Provincial Key Laboratory of Chemical Biology,Tsinghua Shenzhen International Graduate School,Shenzhen 518055,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaLocal Innovative and Research Teams Project of Guangdong Pearl River Talents Program,ChinaNatural Science Foundation of Guangdong Province,ChinaNatural Science Foundation of Guangdong Province,ChinaNatural Science Foundation of Guangdong Province,ChinaNatural Science Foundation of Guangdong Province,ChinaNatural Science Foundation of Guangdong Province,ChinaNatural Science Foundation of Guangdong Province,ChinaMinistry of Science and Technology of ChinaNational highlevel personnel of special support program(Zhang Dongmei)National Key R&D Program of ChinaTechnology Key Project of Guangdong Province,ChinaGuangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research,CollegeSpecial Funds for the Cultivation of Guangdong College Students'Scientifc and Technological Innovation("Climbing Program"SpecialScience and Technology Projects in Guangzhou,ChinaScience and Technology Projects in Guangzhou,ChinaScience and Technology Projects in Guangzhou,ChinaScience and Technology Projects in Guangzhou,ChinaYoung S&T Talent Training Program of Guangdong Provincial Association for S&T,ChinaClinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,ChinaChina Postdoctoral Science Foundation,China

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2024

10.1016/j.apsb.2023.11.002

药学学报(英文版)

药学学报(英文版)

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ISSN：
年,卷(期)：2024.14(2)
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