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

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.
Yating Lu 1 2,  Yang Yang 1 2,  Tao Chang 1 2,  Qiyun Jiang 1 3,  Chenfeng Yang 1 4 5,  Chunzhe Fu 1 6,  Huijun Wei 1 7,  Yuanpeng He 1 2 7,  Zhihao Wu 1 2 7 8 9
Affiliations

Affiliations

  • 1 Research Laboratory of Tumor Microenvironment Wannan Medical College Wuhu China.
  • 2 School of Clinical Medicine Wannan Medical College Wuhu China.
  • 3 School of Public Health Wannan Medical College Wuhu China.
  • 4 School of Pharmacy Wannan Medical College Wuhu China.
  • 5 Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui Wannan Medical College Wuhu China.
  • 6 School of Anesthesiology Wannan Medical College Wuhu China.
  • 7 Anhui Province Key Laboratory of Active Biological Macro-molecules Research Wannan Medical College Wuhu China.
  • 8 Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution Wannan Medical College Wuhu China.
  • 9 Anhui Provincial Engineering Research Center for Dental Materials and Application Wannan Medical College Wuhu China.
PMID: 38545257 DOI: 10.1002/ccs3.12018
Abstract

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.

Keywords

CD38; EMT; Snail; TAZ; lactate; lung cancer.

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