• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

癌症中一种新型葡萄糖代谢的发现：内质网在糖酵解和磷酸戊糖途径之外的作用。

Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt.

作者信息

Marini Cecilia, Ravera Silvia, Buschiazzo Ambra, Bianchi Giovanna, Orengo Anna Maria, Bruno Silvia, Bottoni Gianluca, Emionite Laura, Pastorino Fabio, Monteverde Elena, Garaboldi Lucia, Martella Roberto, Salani Barbara, Maggi Davide, Ponzoni Mirco, Fais Franco, Raffaghello Lizzia, Sambuceti Gianmario

机构信息

CNR Institute of Molecular Bioimaging and Physiology (IBFM), Milan, Section of Genoa, Genoa, Italy.

Nuclear Medicine Unit, Department of Health Sciences, University of Genoa and IRCCS AOU San Martino-IST, Genoa, Italy.

出版信息

Sci Rep. 2016 Apr 28;6:25092. doi: 10.1038/srep25092.

DOI:10.1038/srep25092
PMID:27121192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4848551/
Abstract

Cancer metabolism is characterized by an accelerated glycolytic rate facing reduced activity of oxidative phosphorylation. This "Warburg effect" represents a standard to diagnose and monitor tumor aggressiveness with (18)F-fluorodeoxyglucose whose uptake is currently regarded as an accurate index of total glucose consumption. Studying cancer metabolic response to respiratory chain inhibition by metformin, we repeatedly observed a reduction of tracer uptake facing a marked increase in glucose consumption. This puzzling discordance brought us to discover that (18)F-fluorodeoxyglucose preferentially accumulates within endoplasmic reticulum by exploiting the catalytic function of hexose-6-phosphate-dehydrogenase. Silencing enzyme expression and activity decreased both tracer uptake and glucose consumption, caused severe energy depletion and decreased NADPH content without altering mitochondrial function. These data document the existence of an unknown glucose metabolism triggered by hexose-6-phosphate-dehydrogenase within endoplasmic reticulum of cancer cells. Besides its basic relevance, this finding can improve clinical cancer diagnosis and might represent potential target for therapy.

摘要

癌症代谢的特征是糖酵解速率加快，而氧化磷酸化活性降低。这种“瓦伯格效应”是用（18）F-氟脱氧葡萄糖诊断和监测肿瘤侵袭性的标准，其摄取目前被视为总葡萄糖消耗的准确指标。在研究二甲双胍对呼吸链抑制的癌症代谢反应时，我们反复观察到示踪剂摄取减少，而葡萄糖消耗显著增加。这种令人费解的不一致促使我们发现，（18）F-氟脱氧葡萄糖通过利用己糖-6-磷酸脱氢酶的催化功能优先在内质网中积累。沉默酶的表达和活性会降低示踪剂摄取和葡萄糖消耗，导致严重的能量消耗和NADPH含量降低，而不会改变线粒体功能。这些数据证明了癌细胞内质网中由己糖-6-磷酸脱氢酶触发的未知葡萄糖代谢的存在。除了其基本相关性外，这一发现可以改善临床癌症诊断，并可能代表潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/88d58ad77ccd/srep25092-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/7e82f56dfd96/srep25092-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/947513c1896d/srep25092-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/c9d478a6fffb/srep25092-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/231b9bfed887/srep25092-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/f24bdf0aca09/srep25092-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/88d58ad77ccd/srep25092-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/7e82f56dfd96/srep25092-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/947513c1896d/srep25092-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/c9d478a6fffb/srep25092-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/231b9bfed887/srep25092-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/f24bdf0aca09/srep25092-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f13/4848551/88d58ad77ccd/srep25092-f6.jpg

相似文献

1
Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt.癌症中一种新型葡萄糖代谢的发现：内质网在糖酵解和磷酸戊糖途径之外的作用。
Sci Rep. 2016 Apr 28;6:25092. doi: 10.1038/srep25092.
2
Metformin and Cancer Glucose Metabolism: At the Bench or at the Bedside?二甲双胍与癌症葡萄糖代谢：处于实验阶段还是临床应用阶段？
Biomolecules. 2021 Aug 18;11(8):1231. doi: 10.3390/biom11081231.
3
Obligatory role of endoplasmic reticulum in brain FDG uptake.内质网在脑 FDG 摄取中的必需作用。
Eur J Nucl Med Mol Imaging. 2019 May;46(5):1184-1196. doi: 10.1007/s00259-018-4254-2. Epub 2019 Jan 8.
4
Reduced cellular Mg²⁺ content enhances hexose 6-phosphate dehydrogenase activity and expression in HepG2 and HL-60 cells.细胞内镁离子含量降低可增强 HepG2 和 HL-60 细胞中己糖 6-磷酸脱氢酶的活性和表达。
Arch Biochem Biophys. 2014 Apr 15;548:11-9. doi: 10.1016/j.abb.2014.02.016. Epub 2014 Mar 11.
5
Hexose-6-phosphate dehydrogenase: linking endocrinology and metabolism in the endoplasmic reticulum.己糖-6-磷酸脱氢酶：在内质网中连接内分泌学与代谢
J Mol Endocrinol. 2009 Apr;42(4):283-9. doi: 10.1677/JME-08-0156. Epub 2008 Dec 5.
6
Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation.细胞能量代谢的标准模型是否需要重新考虑？戊糖磷酸途径、糖酵解和细胞外氧化磷酸化之间可能存在偶联。
Biochimie. 2024 Jun;221:99-109. doi: 10.1016/j.biochi.2024.01.018. Epub 2024 Feb 1.
7
Impact of nitric oxide on macrophage glucose metabolism and glyceraldehyde-3-phosphate dehydrogenase activity.一氧化氮对巨噬细胞葡萄糖代谢及3-磷酸甘油醛脱氢酶活性的影响
Am J Physiol. 1995 Mar;268(3 Pt 1):C669-75. doi: 10.1152/ajpcell.1995.268.3.C669.
8
18F-Fluorodeoxyglucose Positron Emission Tomography Tracks the Heterogeneous Brain Susceptibility to the Hyperglycemia-Related Redox Stress.18F-氟代脱氧葡萄糖正电子发射断层扫描追踪大脑对高血糖相关氧化应激的异质性易感性。
Int J Mol Sci. 2020 Oct 31;21(21):8154. doi: 10.3390/ijms21218154.
9
Metabolic phenotype of bladder cancer.膀胱癌的代谢表型。
Cancer Treat Rev. 2016 Apr;45:46-57. doi: 10.1016/j.ctrv.2016.03.005. Epub 2016 Mar 8.
10
Two high-rate pentose-phosphate pathways in cancer cells.癌细胞中有两条高活性戊糖磷酸途径。
Sci Rep. 2020 Dec 17;10(1):22111. doi: 10.1038/s41598-020-79185-2.

引用本文的文献

1
The Imaging Value of F-FAPI PET/CT in Sorafenib-Induced Cardiac Dysfunction in Patients with Hepatocellular Carcinoma: Compared with F-FDG PET/CT.F-FAPI PET/CT在肝细胞癌患者索拉非尼诱导的心脏功能障碍中的成像价值：与F-FDG PET/CT的比较
Mol Imaging Biol. 2025 Apr 30. doi: 10.1007/s11307-025-02005-4.
2
Localized FDG loss in lung cancer lesions.肺癌病灶中局部FDG摄取缺失
EJNMMI Res. 2024 Nov 1;14(1):102. doi: 10.1186/s13550-024-01161-y.
3
Mandatory role of endoplasmic reticulum in preserving NADPH regeneration in starved MDA-MB-231 breast cancer cells.

本文引用的文献

1
Divergent targets of glycolysis and oxidative phosphorylation result in additive effects of metformin and starvation in colon and breast cancer.糖酵解和氧化磷酸化的不同靶点导致二甲双胍和饥饿在结肠癌和乳腺癌中产生累加效应。
Sci Rep. 2016 Jan 22;6:19569. doi: 10.1038/srep19569.
2
Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells.二甲双胍抑制B细胞慢性淋巴细胞白血病细胞的细胞周期进程。
Oncotarget. 2015 Sep 8;6(26):22624-40. doi: 10.18632/oncotarget.4168.
3
Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models.
内质网在饥饿的MDA-MB-231乳腺癌细胞中维持NADPH再生方面的关键作用。
Heliyon. 2024 Sep 28;10(19):e38718. doi: 10.1016/j.heliyon.2024.e38718. eCollection 2024 Oct 15.
4
The pivotal role of endoplasmic reticulum in FDG uptake in cancer cells.内质网在癌细胞摄取氟代脱氧葡萄糖（FDG）中的关键作用。
EJNMMI Res. 2024 Jul 12;14(1):64. doi: 10.1186/s13550-024-01124-3.
5
The Liaison between Metabolism and Oxidative Stress in Human Diseases.代谢与氧化应激在人类疾病中的联系。
Cells. 2023 Dec 12;12(24):2823. doi: 10.3390/cells12242823.
6
Mandatory role of endoplasmic reticulum and its pentose phosphate shunt in the myocardial defense mechanisms against the redox stress induced by anthracyclines.内质网及其戊糖磷酸途径在心肌对抗蒽环类药物诱导的氧化还原应激防御机制中的强制性作用。
Mol Cell Biochem. 2024 Nov;479(11):2973-2987. doi: 10.1007/s11010-023-04903-z. Epub 2023 Dec 12.
7
A fingerprint of 2-[F]FDG radiometabolites - How tissue-specific metabolism beyond 2-[F]FDG-6-P could affect tracer accumulation.2-[F]FDG放射性代谢物的指纹图谱——2-[F]FDG-6-P之外的组织特异性代谢如何影响示踪剂积累。
iScience. 2023 Oct 6;26(11):108137. doi: 10.1016/j.isci.2023.108137. eCollection 2023 Nov 17.
8
Divergent Oxidative Stress in Normal Tissues and Inflammatory Cells in Hodgkin and Non-Hodgkin Lymphoma.霍奇金淋巴瘤和非霍奇金淋巴瘤中正常组织与炎症细胞的不同氧化应激
Cancers (Basel). 2023 Jul 7;15(13):3533. doi: 10.3390/cancers15133533.
9
CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NAD-Lowering Agents.CD38诱导的代谢功能障碍使多发性骨髓瘤细胞对降低NAD的药物敏感。
Antioxidants (Basel). 2023 Feb 15;12(2):494. doi: 10.3390/antiox12020494.
10
Fundamental Role of Pentose Phosphate Pathway within the Endoplasmic Reticulum in Glutamine Addiction of Triple-Negative Breast Cancer Cells.内质网中磷酸戊糖途径在三阴性乳腺癌细胞谷氨酰胺成瘾中的基本作用
Antioxidants (Basel). 2022 Dec 26;12(1):43. doi: 10.3390/antiox12010043.
禁食诱导抗瓦伯格效应，该效应增加呼吸作用但减少ATP合成，从而在结肠癌模型中促进细胞凋亡。
Oncotarget. 2015 May 20;6(14):11806-19. doi: 10.18632/oncotarget.3688.
4
Correlation of Glut-1 glucose transporter expression with [(18)F]FDG uptake in non-small cell lung cancer.非小细胞肺癌中葡萄糖转运蛋白1（Glut-1）表达与[18F]氟代脱氧葡萄糖（FDG）摄取的相关性
Eur J Nucl Med. 2000 Dec;27(12):1778-85. doi: 10.1007/s002590000367.
5
Synergistic anti-cancer effect of phenformin and oxamate.苯乙双胍和草氨酸的协同抗癌作用。
PLoS One. 2014 Jan 21;9(1):e85576. doi: 10.1371/journal.pone.0085576. eCollection 2014.
6
Molecular mechanisms of [18F]fluorodeoxyglucose accumulation in liver cancer.肝癌中[18F]氟脱氧葡萄糖积聚的分子机制。
Oncol Rep. 2014 Feb;31(2):701-6. doi: 10.3892/or.2013.2886. Epub 2013 Nov 29.
7
Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer.二甲双胍直接抑制己糖激酶活性，至少部分损害实验性乳腺癌中的葡萄糖代谢和肿瘤生长。
Cell Cycle. 2013 Nov 15;12(22):3490-9. doi: 10.4161/cc.26461.
8
Metformin impairs glucose consumption and survival in Calu-1 cells by direct inhibition of hexokinase-II.二甲双胍通过直接抑制己糖激酶-II 来损害 Calu-1 细胞的葡萄糖摄取和存活。
Sci Rep. 2013;3:2070. doi: 10.1038/srep02070.
9
Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.范可尼贫血症补体组 A 中存在线粒体呼吸链复合物 I 缺陷。
Biochimie. 2013 Oct;95(10):1828-37. doi: 10.1016/j.biochi.2013.06.006. Epub 2013 Jun 19.
10
Metformin temporal and localized effects on gut glucose metabolism assessed using 18F-FDG PET in mice.采用 18F-FDG PET 在小鼠中评估二甲双胍对肠道葡萄糖代谢的时相和局部作用。
J Nucl Med. 2013 Feb;54(2):259-66. doi: 10.2967/jnumed.112.106666. Epub 2013 Jan 3.