CD73 独立于 GAS6 通过调节 Axl 信号促进非小细胞肺癌转移

IF 9.4 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the National Academy of Sciences of the United States of America Pub Date : 2024-10-18 DOI:10.1073/pnas.2404709121

Jianjie Zhu, Wenwen Du, Yuanyuan Zeng, Ting Liu, Jianjun Li, Anqi Wang, Yue Li, Weijie Zhang, Jian-an Huang, Zeyi Liu

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引用次数: 0

摘要

作为分解酶，CD73能使单磷酸腺苷（AMP）去磷酸化，还能调节肿瘤细胞的增殖和转移。迄今为止，很少有研究探讨 CD73 在介导非小细胞肺癌（NSCLC）转移中的作用，其潜在的传导信号也尚未阐明。在本研究中，我们证实了CD73/Axl轴可调控Smad3诱导的上皮细胞向间质转化（EMT），从而促进NSCLC转移。在机制上，CD73可通过高尔基体转运途径分泌。分泌的CD73可与Axl胞外结构域中的R55位点直接结合，从而激活AXl，而与GAS6无关。此外，我们还证明了 CD73 可通过抑制 CBLB 的表达来稳定 Axl 的表达。我们还发现了 CD73 在腺癌和鳞癌中的不同功能。我们的研究结果表明了 CD73 在介导 NSCLC 转移中的作用，并建议将其作为 NSCLC 的治疗靶点。

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

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 present 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 extracellular 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 indicated a role of CD73 in mediating NSCLC metastasis and propose it as a therapeutic target for NSCLC.

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来源期刊

Proceedings of the National Academy of Sciences of the United States of America 综合性期刊-综合性期刊

CiteScore

19.00

自引率

0.90%

发文量

3575

审稿时长

2.5 months

期刊介绍： The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.