乳酸盐通过蜗牛诱导CD38信号传导，促进非小细胞肺癌细胞的上皮-间质转化

IF 3.6 3区生物学 Q3 CELL BIOLOGY Journal of Cell Communication and Signaling Pub Date : 2024-02-14 DOI:10.1002/ccs3.12018

Yating Lu, Yang Yang, Tao Chang, Qiyun Jiang, Chenfeng Yang, Chunzhe Fu, Huijun Wei, Yuanpeng He, Zhihao Wu

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引用次数: 0

摘要

CD38 是哺乳动物细胞中的主要 NAD 酶。它调节烟酰胺腺嘌呤二核苷酸（NAD+）和细胞外核苷酸的平衡。它的功能在感染和衰老中发挥着重要作用。然而，它在肿瘤细胞中的潜在功能尚未完全阐明。在本研究中，我们证实了肿瘤代谢重塑产生的乳酸可通过 OXPHOS 驱动的 Hippo-TAZ 通路上调 CD38 的表达。高表达的CD38通过CD203a/CD73复合物将NAD +转化为腺苷，腺苷结合并激活其受体A2AR，诱导蜗牛的表达，促进肺癌细胞的侵袭和转移。这一发现从一个新的角度阐明了 NAD + 代谢和糖酵解在肿瘤发生中的相互作用。

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Lactate drives CD38 signaling to promote Epithelial-Mesenchymal Transition through Snail induction in non-small cell lung cancer cells

CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

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来源期刊

Journal of Cell Communication and Signaling CELL BIOLOGY-

CiteScore

6.40

自引率

4.90%

发文量

期刊介绍： The Journal of Cell Communication and Signaling provides a forum for fundamental and translational research. In particular, it publishes papers discussing intercellular and intracellular signaling pathways that are particularly important to understand how cells interact with each other and with the surrounding environment, and how cellular behavior contributes to pathological states. JCCS encourages the submission of research manuscripts, timely reviews and short commentaries discussing recent publications, key developments and controversies. Research manuscripts can be published under two different sections : In the Pathology and Translational Research Section (Section Editor Andrew Leask) , manuscripts report original research dealing with celllular aspects of normal and pathological signaling and communication, with a particular interest in translational research. In the Molecular Signaling Section (Section Editor Satoshi Kubota) manuscripts report original signaling research performed at molecular levels with a particular interest in the functions of intracellular and membrane components involved in cell signaling.