Acta Pharmaceutica Sinica B (Feb 2024)
Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis
- 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
Affiliations
- Shuran Fan
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Ming Qi
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong 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
- Qi Qi
- School of Medicine, Jinan University, Guangzhou 510632, China
- Qun Miao
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Lijuan Deng
- School of Traditional Chinese Medicine, Jinan University, Guangzhou 510630, China
- Jinghua Pan
- The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Shenghui Qiu
- The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Jiashuai He
- The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Maohua Huang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Xiaobo Li
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Jie Huang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Jiapeng Lin
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Wenyu Lyu
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Weiqing Deng
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Yingyin He
- Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China
- Xuesong Liu
- The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Lvfen Gao
- The First Affiliated Hospital of Jinan University, Guangzhou 510632, China; Corresponding authors.
- Dongmei Zhang
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China; Corresponding authors.
- Wencai Ye
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China; Corresponding authors.
- Minfeng Chen
- State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, China; State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China; Corresponding authors.
- Journal volume & issue
-
Vol. 14,
no. 2
pp. 682 – 697
Abstract
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.
