• 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

微转移灶的代谢适应改变了细胞外囊泡的产生，从而形成侵袭性微环境。

Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments.

作者信息

Gounis Michalis, Campos America V, Shokry Engy, Mitchell Louise, Deshmukh Ruhi, Dornier Emmanuel, Rooney Nicholas, Dhayade Sandeep, Pardo Luis, Moore Madeleine, Novo David, Mowat Jenna, Jamieson Craig, Kay Emily, Zanivan Sara, Paul Nikki R, Mitchell Claire, Nixon Colin, Macpherson Iain, Tardito Saverio, Sumpton David, Blyth Karen, Norman Jim C, Clarke Cassie J

机构信息

Cancer Research UK Scotland Institute , Glasgow, UK.

School of Cancer Sciences, University of Glasgow , Glasgow, UK.

出版信息

J Cell Biol. 2025 Aug 4;224(8). doi: 10.1083/jcb.202405061. Epub 2025 Jun 9.

DOI:10.1083/jcb.202405061
PMID:40488669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12147664/
Abstract

Altered cellular metabolism has been associated with the acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model of mammary carcinoma with syngeneic transplantation and primary tumor resection to generate isogenic cells from primary tumors and their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic cells increase proline production at the expense of glutathione synthesis, leading to a reduction in total glutathione levels. Micrometastatic cells also have altered sphingomyelin metabolism, leading to increased intracellular levels of specific ceramides. The combination of these metabolic adaptations alters extracellular vesicle (EV) production to render the microenvironment more permissive for invasion. Indeed, micrometastatic cells shut down Rab27-dependent production of EVs and, instead, switch on neutral sphingomyelinase-2 (nSM2)-dependent EV release. EVs released in an nSM2-dependent manner from micrometastatic cells, in turn, influence the ability of fibroblasts to deposit extracellular matrix, which promotes cancer cell invasiveness. These data provide evidence that metabolic rewiring drives invasive processes in metastasis by influencing EV release.

摘要

细胞代谢改变与转移过程中侵袭性表型的获得有关。为了研究这一点，我们将一种基因工程小鼠乳腺癌模型与同基因移植和原发性肿瘤切除相结合，以从原发性肿瘤及其相应的肺微转移灶中产生同基因细胞。代谢分析表明，微转移细胞以谷胱甘肽合成减少为代价增加脯氨酸的产生，导致总谷胱甘肽水平降低。微转移细胞的鞘磷脂代谢也发生改变，导致特定神经酰胺的细胞内水平升高。这些代谢适应性变化共同改变细胞外囊泡（EV）的产生，使微环境更有利于侵袭。事实上，微转移细胞关闭了Rab27依赖的EV产生，转而开启中性鞘磷脂酶-2（nSM2）依赖的EV释放。微转移细胞以nSM2依赖的方式释放的EV反过来又影响成纤维细胞沉积细胞外基质的能力，从而促进癌细胞的侵袭。这些数据提供了证据，表明代谢重编程通过影响EV释放驱动转移中的侵袭过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/1d559160b1a7/jcb_202405061_figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/7d92c41af41c/jcb_202405061_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f8f5a2d7176b/jcb_202405061_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/5e9151f83f62/jcb_202405061_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/65244b78db90/jcb_202405061_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/6264c47be3b0/jcb_202405061_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/3bbe8e5b8d2b/jcb_202405061_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/b15591ec8c4c/jcb_202405061_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f5fd4303ff4b/jcb_202405061_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/249d00e1af68/jcb_202405061_figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/ea4de1f4a8f7/jcb_202405061_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/e66bb9c8f024/jcb_202405061_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f7e09d962d38/jcb_202405061_figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/1d559160b1a7/jcb_202405061_figs5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/7d92c41af41c/jcb_202405061_fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f8f5a2d7176b/jcb_202405061_fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/5e9151f83f62/jcb_202405061_fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/65244b78db90/jcb_202405061_figs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/6264c47be3b0/jcb_202405061_fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/3bbe8e5b8d2b/jcb_202405061_fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/b15591ec8c4c/jcb_202405061_figs2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f5fd4303ff4b/jcb_202405061_fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/249d00e1af68/jcb_202405061_figs3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/ea4de1f4a8f7/jcb_202405061_fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/e66bb9c8f024/jcb_202405061_fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/f7e09d962d38/jcb_202405061_figs4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d41/12147664/1d559160b1a7/jcb_202405061_figs5.jpg

相似文献

1
Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments.微转移灶的代谢适应改变了细胞外囊泡的产生，从而形成侵袭性微环境。
J Cell Biol. 2025 Aug 4;224(8). doi: 10.1083/jcb.202405061. Epub 2025 Jun 9.
2
Fibroblast proximity to a tumor impacts fibroblast extracellular vesicles produced by 3D bioprinted stromal models.成纤维细胞与肿瘤的接近程度会影响由3D生物打印基质模型产生的成纤维细胞细胞外囊泡。
Biomater Sci. 2025 Jun 10. doi: 10.1039/d4bm01569j.
3
Isolation and characterization of bone mesenchymal cell small extracellular vesicles using a novel mouse model.利用新型小鼠模型分离和鉴定骨髓间充质细胞的小细胞外囊泡。
J Bone Miner Res. 2024 Oct 29;39(11):1633-1643. doi: 10.1093/jbmr/zjae135.
4
Human Infrapatellar Fat Pad Mesenchymal Stem Cell-derived Extracellular Vesicles Purified by Anion Exchange Chromatography Suppress Osteoarthritis Progression in a Mouse Model.阴离子交换层析法纯化的人髌下脂肪垫间充质干细胞来源细胞外囊泡抑制骨关节炎在小鼠模型中的进展。
Clin Orthop Relat Res. 2024 Jul 1;482(7):1246-1262. doi: 10.1097/CORR.0000000000003067. Epub 2024 Apr 19.
5
Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.两种现代生存预测工具 SORG-MLA 和 METSSS 在接受手术联合放疗和单纯放疗治疗有症状长骨转移患者中的比较。
Clin Orthop Relat Res. 2024 Dec 1;482(12):2193-2208. doi: 10.1097/CORR.0000000000003185. Epub 2024 Jul 23.
6
The Black Book of Psychotropic Dosing and Monitoring.《精神药物剂量与监测黑皮书》
Psychopharmacol Bull. 2024 Jul 8;54(3):8-59.
7
Quantitative characterisation of extracellular vesicles designed to decoy or compete with SARS-CoV-2 reveals differential mode of action across variants of concern and highlights the diversity of Omicron.旨在与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）诱饵或竞争的细胞外囊泡的定量表征揭示了针对不同关注变体的不同作用模式，并突出了奥密克戎的多样性。
Cell Commun Signal. 2025 Jul 2;23(1):323. doi: 10.1186/s12964-025-02223-x.
8
HIF-1 promotes murine breast cancer brain metastasis by increasing production of integrin β3-containing extracellular vesicles.缺氧诱导因子-1通过增加含整合素β3的细胞外囊泡的产生来促进小鼠乳腺癌脑转移。
J Clin Invest. 2025 Jul 15;135(14). doi: 10.1172/JCI190470.
9
Extracellular vesicles: the "Trojan Horse" within breast cancer host microenvironments.细胞外囊泡：乳腺癌宿主微环境中的“特洛伊木马”。
Mol Cancer. 2025 Jun 23;24(1):183. doi: 10.1186/s12943-025-02358-y.
10
Short-Term Memory Impairment短期记忆障碍

引用本文的文献

1
Uridine phosphorylase-1 supports metastasis by altering immune and extracellular matrix landscapes.尿苷磷酸化酶-1通过改变免疫和细胞外基质环境来支持转移。
EMBO Rep. 2025 Jul 23. doi: 10.1038/s44319-025-00520-7.

本文引用的文献

1
Mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade response in melanoma.线粒体 DNA 突变驱动有氧糖酵解以增强黑色素瘤的检查点封锁反应。
Nat Cancer. 2024 Apr;5(4):659-672. doi: 10.1038/s43018-023-00721-w. Epub 2024 Jan 29.
2
Loss of attachment promotes proline accumulation and excretion in cancer cells.失巢凋亡促进肿瘤细胞脯氨酸积累和排出。
Sci Adv. 2023 Sep 8;9(36):eadh2023. doi: 10.1126/sciadv.adh2023. Epub 2023 Sep 6.
3
SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells.
SLC7A11 的表达水平决定了癌细胞对氧化应激的不同反应。
Nat Commun. 2023 Jun 21;14(1):3673. doi: 10.1038/s41467-023-39401-9.
4
Tumour extracellular vesicles and particles induce liver metabolic dysfunction.肿瘤细胞外囊泡和颗粒诱导肝脏代谢功能障碍。
Nature. 2023 Jun;618(7964):374-382. doi: 10.1038/s41586-023-06114-4. Epub 2023 May 24.
5
Transwell In Vitro Cell Migration and Invasion Assays.Transwell 体外细胞迁移和侵袭实验。
Methods Mol Biol. 2023;2644:349-359. doi: 10.1007/978-1-0716-3052-5_22.
6
Hepatic glutamine synthetase controls N-methylglutamine in homeostasis and cancer.肝脏谷氨酰胺合成酶控制着 N-甲基谷氨酸在体内平衡和癌症中的作用。
Nat Chem Biol. 2023 Mar;19(3):292-300. doi: 10.1038/s41589-022-01154-9. Epub 2022 Oct 24.
7
Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures.转移性三阴性乳腺癌在保留关键代谢特征的同时，使其代谢适应靶组织。
Proc Natl Acad Sci U S A. 2022 Aug 30;119(35):e2205456119. doi: 10.1073/pnas.2205456119. Epub 2022 Aug 22.
8
Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix.癌相关成纤维细胞需要 PYCR1 来合成脯氨酸，以沉积促肿瘤生成的细胞外基质。
Nat Metab. 2022 Jun;4(6):693-710. doi: 10.1038/s42255-022-00582-0. Epub 2022 Jun 27.
9
Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions.脯氨酸通过 PYCR1 的合成对于在缺氧条件下支持癌细胞的增殖和存活是必需的。
Cell Rep. 2022 Feb 1;38(5):110320. doi: 10.1016/j.celrep.2022.110320.
10
Plasma Metabolomics and Breast Cancer Risk over 20 Years of Follow-up among Postmenopausal Women in the Nurses' Health Study.绝经后妇女 20 年随访中的血浆代谢组学与乳腺癌风险：护士健康研究。
Cancer Epidemiol Biomarkers Prev. 2022 Apr 1;31(4):839-850. doi: 10.1158/1055-9965.EPI-21-1023.