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

J Cell Commun Signal. 2024 Feb 14;18(1):e12018. doi: 10.1002/ccs3.12018. eCollection 2024 Mar.ABSTRACTCD38 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.PMID:38545257 | PMC:PMC10964942 | DOI:10.1002/ccs3.12018

Source: Journal of Cell Communication and Signaling - March 28, 2024 Category: Molecular Biology Authors: Yating Lu Yang Yang Tao Chang Qiyun Jiang Chenfeng Yang Chunzhe Fu Huijun Wei Yuanpeng He Zhihao Wu Source Type: research