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

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.

01 Mar 2023·Acta Pharmaceutica Sinica B

Author correction to “The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway” [Acta Pharm Sin B 12 (2022) 1288–1304]

Author: Li, Xiaobo ; Li, Yong ; Ye, Geni ; Zhang, Dongmei ; Huang, Maohua ; Chen, Minfeng ; Zeng, Huhu ; Weng, Qing ; Long, Pei ; Yin, Junqiang ; Ye, Wencai ; Ouyang, Jie ; Fan, Zepei

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

01 Mar 2022·Acta Pharmaceutica Sinica BQ1 · CHEMISTRY

The FAP -activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway

Q1 · CHEMISTRY

ArticleOA

Author: Li, Xiaobo ; Li, Yong ; Huang, Maohua ; Zhang, Dongmei ; Zeng, Huhu ; Chen, Minfeng ; Wen, Qing ; Yin, Junqiang ; Long, Pei ; Ye, Geni ; Ye, Wencai ; Ouyang, Jie ; Fan, Zepei

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	China	Jinan University	28 Aug 2017

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