Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation
文献类型：期刊论文
| 作者 | Chen, Man-man1,3; Guo, Wei1,3; Chen, Si-meng3; Guo, Xiao-zhen2; Xu, Lan3; Ma, Xiao-yu1,3; Wang, Yu-xiang3; Xie, Cen1,2 ; Meng, Ling-hua1,3
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| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2023 |
| 卷号 | 19期号:3页码:772-788 |
| 关键词 | Xanthine dehydrogenase nucleoside degradation cell survival UPR autophagy LUAD |
| DOI | 10.7150/ijbs.78948 |
| 文献子类 | Article |
| 英文摘要 | Xanthine dehydrogenase (XDH) is the rate-limiting enzyme in purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. The altered expression and activity of XDH are associated with the development and prognosis of multiple types of cancer, while its role in lung adenocarcinoma (LUAD) remains unknown. Herein, we demonstrated that XDH was highly expressed in LUAD and was significantly correlated with poor prognosis. Though inhibition of XDH displayed moderate effect on the viability of LUAD cells cultured in the complete medium, it significantly attenuated the survival of starved cells. Similar results were obtained in XDH-knockout cells. Nucleosides supplementation rescued the survival of starved LUAD cells upon XDH inhibition, while inhibition of purine nucleoside phosphorylase abrogated the process, indicating that nucleoside degradation is required for the XDH-mediated survival of LUAD cells. Accordingly, metabolic flux revealed that ribose derived from nucleoside fueled key carbon metabolic pathways to sustain the survival of starved LUAD cells. Mechanistically, down-regulation of XDH suppressed unfolded protein response (UPR) and autophagic flux in starved LUAD cells. Inhibition of XDH decreased the level of amino acids produced by autophagic degradation, which was accompanied with down-regulation of mTORC1 signaling. Supplementation of amino acids including glutamine or glutamate rescued the survival of starved LUAD cells upon knockout or inhibition of XDH. Finally, XDH inhibitors potentiated the anti-cancer activity of 2-deoxy-D-glucose that induced UPR and/or autophagy in vitro and in vivo. In summary, XDH plays a crucial role in the survival of starved LUAD cells and targeting XDH may improve the efficacy of drugs that induce UPR and autophagy in the therapy of LUAD. |
| WOS关键词 | TARGETING METABOLISM ; EMERGING ROLE ; CANCER ; OXIDOREDUCTASE ; PROTEIN ; INHIBITION ; MAINTENANCE ; EXPRESSION ; RESISTANCE ; OXIDASE |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000935312600003 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309724]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Meng, Ling-hua |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, 501 Haike Rd, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Chen, Man-man,Guo, Wei,Chen, Si-meng,et al. Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023,19(3):772-788. |
| APA | Chen, Man-man.,Guo, Wei.,Chen, Si-meng.,Guo, Xiao-zhen.,Xu, Lan.,...&Meng, Ling-hua.(2023).Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19(3),772-788. |
| MLA | Chen, Man-man,et al."Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19.3(2023):772-788. |
入库方式： OAI收割
来源：上海药物研究所
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