دورية أكاديمية
Dihydroartemisinin breaks the positive feedback loop of YAP1 and GLUT1-mediated aerobic glycolysis to boost the CD8 + effector T cells in hepatocellular carcinoma.
| العنوان: | Dihydroartemisinin breaks the positive feedback loop of YAP1 and GLUT1-mediated aerobic glycolysis to boost the CD8 + effector T cells in hepatocellular carcinoma. |
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| المؤلفون: | Gao Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China., Gong Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China., Lu J; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China., Yang Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China., Zhang Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China., Xiong Y; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China., Shi X; Laboratory of Integrated Medicine Tumor Immunology, Shanxi University of Chinese Medicine, Taiyuan 030000, China; Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China. Electronic address: shixinli@sxtcm.edu.cn. |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2024 Jul; Vol. 225, pp. 116294. Date of Electronic Publication: 2024 May 14. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | Artemisinins*/pharmacology , Carcinoma, Hepatocellular*/metabolism , Carcinoma, Hepatocellular*/drug therapy , Carcinoma, Hepatocellular*/pathology , Glucose Transporter Type 1*/metabolism , Glucose Transporter Type 1*/genetics , Glucose Transporter Type 1*/antagonists & inhibitors , Glycolysis*/drug effects , Glycolysis*/physiology , Liver Neoplasms*/metabolism , Liver Neoplasms*/drug therapy , Liver Neoplasms*/pathology , YAP-Signaling Proteins*/metabolism, Animals ; Humans ; Mice ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Feedback, Physiological/drug effects ; Cell Line, Tumor ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Male ; Mice, Inbred C57BL |
| مستخلص: | Aerobic glycolysis is a hallmark of hepatocellular carcinoma (HCC). Dihydroartemisinin (DHA) exhibits antitumor activity towards liver cancer. Our previous studies have shown that DHA inhibits the Warburg effect in HCC cells. However, the mechanism still needs to be clarified. Our study aimed to elucidate the interaction between YAP1 and GLUT1-mediated aerobic glycolysis in HCC cells and focused on the underlying mechanisms of DHA inhibiting aerobic glycolysis in HCC cells. In this study, we confirmed that inhibition of YAP1 expression lowers GLUT1-mediated aerobic glycolysis in HCC cells and enhances the activity of CD8 + T cells in the tumor niche. Then, we found that DHA was bound to cellular YAP1 in HCC cells. YAP1 knockdown inhibited GLUT1-mediated aerobic glycolysis, whereas YAP1 overexpression promoted GLUT1-mediated aerobic glycolysis in HCC cells. Notably, liver-specific Yap1 knockout by AAV8-TBG-Cre suppressed HIF-1α and GLUT1 expression in tumors but not para-tumors in DEN/TCPOBOP-induced HCC mice. Even more crucial is that YAP1 forms a positive feedback loop with GLUT1-mediated aerobic glycolysis, which is associated with HIF-1α in HCC cells. Finally, DHA reduced GLUT1-aerobic glycolysis in HCC cells through YAP1 and prevented the binding of YAP1 and HIF-1α. Collectively, our study revealed the mechanism of DHA inhibiting glycolysis in HCC cells from a perspective of a positive feedback loop involving YAP1 and GLUT1 mediated-aerobic glycolysis and provided a feasible therapeutic strategy for targeting enhanced aerobic glycolysis in HCC. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: CD8(+) T cells; Dihydroartemisinin; GLUT1-mediated aerobic glycolysis; Hepatocellular carcinoma; YAP1 |
| المشرفين على المادة: | 0 (Artemisinins) 6A9O50735X (artenimol) 0 (Glucose Transporter Type 1) 0 (YAP-Signaling Proteins) 0 (YAP1 protein, human) 0 (Adaptor Proteins, Signal Transducing) 0 (SLC2A1 protein, human) 0 (Transcription Factors) 0 (Yap1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240614 Latest Revision: 20240910 |
| رمز التحديث: | 20240910 |
| DOI: | 10.1016/j.bcp.2024.116294 |
| PMID: | 38754557 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2024.116294 |