CD73 promotes non-small cell lung cancer metastasis by regulating Axl signaling independent of GAS6

• 成果类型: Article
• 署名作者: Zhu, Jianjie; Du, Wenwen; Zeng, Yuanyuan; Liu, Ting; Li, Jianjun; Wang, Anqi; Li, Yue; Zhang, Weijie; Huang, Jian-an; Liu, Zeyi
• 署名单位: Soochow University - China; Soochow University - China
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11114
• DOI: 10.1073/pnas.2404709121
• 发表日期: 2024-10-22
• 关键词: adenosine

摘要

As catabolic enzyme, CD73 dephosphorylates adenosine monophosphate (AMP) and can also regulate tumor cell proliferation and metastasis. To date, very few studies have explored the role of CD73 in mediating non-small cell lung cancer (NSCLC) metastasis, and the underlying transducing signal has not been elucidated. In the pres- ent study, we demonstrated that the CD73/Axl axis could regulate Smad3-- induced epithelial-- to-- mesenchymal transition (EMT) to promote NSCLC metastasis. Mechanically, CD73 can be secreted via the Golgi apparatus transport pathway. Then secreted CD73 may activate AXl by directly bind with site R55 located in Axl extracel- lular domain independently of GAS6. In addition, we proved that CD73 can stabilize Axl expression via inhibiting CBLB expression. We also identified the distinct function of CD73 activity in adenocarcinoma and squamous cell carcinoma. Our findings indi- cated a role of CD73 in mediating NSCLC metastasis and propose it as a therapeutic target for NSCLC.