دورية أكاديمية
Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells.
| العنوان: | Hypoxia exposure induces lactylation of Axin1 protein to promote glycolysis of esophageal carcinoma cells. |
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| المؤلفون: | Li Q; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China; Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China., Lin G; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Zhang K; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Liu X; Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China., Li Z; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Bing X; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Nie Z; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Jin S; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China., Guo J; School of Medical Technology, Beijing Institute of Technology, Beijing, China. Electronic address: guojin@bit.edu.cn., Min X; Department of Thoracic Surgery, China Aerospace Science and Industry Corporation 731 Hospital, Beijing, China. Electronic address: minxianjun@163.com. |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2024 Aug; Vol. 226, pp. 116415. Date of Electronic Publication: 2024 Jul 06. |
| نوع المنشور: | Journal Article |
| 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: | Axin Protein*/metabolism , Axin Protein*/genetics , Esophageal Neoplasms*/metabolism , Esophageal Neoplasms*/pathology , Glycolysis*/physiology , Mice, Nude*, Humans ; Animals ; Cell Line, Tumor ; Mice ; Mice, Inbred BALB C ; Cell Hypoxia/physiology |
| مستخلص: | The hypoxic microenvironment in esophageal carcinoma is an important factor promoting the rapid progression of malignant tumor. This study was to investigate the lactylation of Axin1 on glycolysis in esophageal carcinoma cells under hypoxia exposure. Hypoxia treatment increases pan lysine lactylation (pan-kla) levels of both TE1 and EC109 cells. Meanwhile, ECAR, glucose consumption and lactate production were also upregulated in both TE1 and EC109 cells. The expression of embryonic stem cell transcription factors NANOG and SOX2 were enhanced in the hypoxia-treated cells. Axin1 overexpression partly reverses the induction effects of hypoxia treatment in TE1 and EC109 cells. Moreover, lactylation of Axin1 protein at K147 induced by hypoxia treatment promotes ubiquitination modification of Axin1 protein to promote glycolysis and cell stemness of TE1 and EC109 cells. Mutant Axin1 can inhibit ECAR, glucose uptake, lactate secretion, and cell stemness in TE1 and EC109 cells under normal or hypoxia conditions. Meanwhile, mutant Axin1 further enhanced the effects of 2-DG on inhibiting glycolysis and cell stemness. Overexpression of Axin1 also inhibited tumor growth in vivo, and was related to suppressing glycolysis. In conclusion, hypoxia treatment promoted the glycolysis and cell stemness of esophageal carcinoma cells, and increased the lactylation of Axin1 protein. Overexpression of Axin1 functioned as a glycolysis inhibitor, and suppressed the effects of hypoxia exposure in vitro and inhibited tumor growth in vivo. Mechanically, hypoxia induces the lactylation of Axin1 protein and promotes the ubiquitination of Axin1 to degrade the protein, thereby exercising its anti-glycolytic function. 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 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Axin1; Esophageal carcinoma; Glycolysis; Hypoxia; Lactylation; Ubiquitination |
| المشرفين على المادة: | 0 (Axin Protein) 0 (AXIN1 protein, human) |
| تواريخ الأحداث: | Date Created: 20240707 Date Completed: 20240725 Latest Revision: 20240729 |
| رمز التحديث: | 20240730 |
| DOI: | 10.1016/j.bcp.2024.116415 |
| PMID: | 38972426 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2024.116415 |