An NF-κB/OVOL2 circuit regulates glucose import and cell survival in non-small cell lung cancer.

Autor: Zhang R; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Geng GJ; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Guo JG; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361100, Fujian, China., Mi YJ; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Zhu XL; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Li N; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Liu HM; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Lin JF; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Wang JW; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Zhao G; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Ye GZ; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China., Li BA; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361100, Fujian, China. bali@xmu.edu.cn.; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361100, Fujian, China. bali@xmu.edu.cn., Luo QC; Laboratory of Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China. qcluo@xmu.edu.cn., Jiang J; Department of Thoracic Surgery and Xiamen Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, China. jjiang59@xmu.edu.cn.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2022 Mar 28; Vol. 20 (1), pp. 40. Date of Electronic Publication: 2022 Mar 28.
DOI: 10.1186/s12964-022-00845-z
Abstrakt: Background: Tumor cells tend to utilize glycolysis rather than aerobic respiration even under aerobic conditions. OVOL2, an inhibitory C2H2 zinc finger transcription factor, is a potential tumor suppressor in cancers. However, the association between OVOL2 and tumor energy metabolism is unknown.
Methods: Western blotting was used to determine the expression of OVOL2 in different non-small cell lung cancer (NSCLC) cell lines and mouse models. The metabolic parameters in NSCLC cells following overexpression or knockdown OVOL2 were examined. To define the mechanism by which OVOL2 regulates aerobic glycolysis, interacting protein of OVOl2 and downstream molecular events were identified by luciferase assay and co-immunoprecipitation. We documented the regulatory mechanism in mouse xenograft models. Finally, clinical relevance of OVOL2, NF-κB signaling and GLUT1 was measured by immunostaining.
Results: OVOL2 is downregulated in NSCLC and overexpression of OVOL2 inhibits the survival of cancer cells. Moreover, OVOL2 directly binds to P65 and inhibits the recruitment of P300 but facilitates the binding of HDAC1 to P65, which in turn negatively regulates NF-κB signaling to suppress GLUT1 translocation and glucose import. In contrast, OVOL2 expression is negatively regulated by NF-κB signaling in NSCLC cells via the ubiquitin-proteasome pathway. Re-expression of OVOL2 significantly compromise NF-κB signaling-induced GLUT1 translocation, aerobic glycolysis in NSCLC cells and mouse models. Immunostaining revealed inverse correlations between the OVOL2 and phosphorylated P65 levels and between the OVOL2 and membrane GLUT1 levels, and a strong correlation between the phosphorylated P65 and membrane GLUT1 levels.
Conclusions: These results suggest a regulatory circuit linking NF-κB and OVOL2, which highlights the role of NF-κB signaling and OVOL2 in the modulation of glucose metabolism in NSCLC. Video Abstract.
(© 2022. The Author(s).)
Databáze: MEDLINE
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