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线粒体复合物 I 促进肾癌转移。

Mitochondrial complex I promotes kidney cancer metastasis.

机构信息

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

Nature. 2024 Sep;633(8031):923-931. doi: 10.1038/s41586-024-07812-3. Epub 2024 Aug 14.

DOI:10.1038/s41586-024-07812-3
PMID:39143213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11424252/
Abstract

Most kidney cancers are metabolically dysfunctional, but how this dysfunction affects cancer progression in humans is unknown. We infused C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming. Compared with the adjacent kidney, clear cell renal cell carcinomas (ccRCCs) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in ex vivo organotypic cultures, indicating that suppressed labelling is tissue intrinsic. [1,2-C]acetate and [U-C]glutamine infusions in patients, coupled with measurements of respiration in isolated human kidney and tumour mitochondria, reveal lower electron transport chain activity in ccRCCs that contributes to decreased oxidative and enhanced reductive TCA cycle labelling. However, ccRCC metastases unexpectedly have enhanced TCA cycle labelling compared with that of primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, whereas inhibiting electron transport chain complex I decreases metastasis. These findings in humans and mice indicate that metabolic properties and liabilities evolve during kidney cancer progression, and that mitochondrial function is limiting for metastasis but not growth at the original site.

摘要

大多数肾癌的代谢功能失调，但这种功能障碍如何影响人类癌症的进展尚不清楚。我们在 80 多名肾癌患者的手术肿瘤切除过程中输注了带[U-C]标记的营养物质。[U-C]葡萄糖的标记在不同亚型之间存在差异，表明肾脏环境本身并不能解释所有肿瘤的代谢重编程。与相邻的肾脏相比，透明细胞肾细胞癌（ccRCC）在体内和离体器官型培养物中显示出三羧酸（TCA）循环中间产物标记的抑制，表明抑制标记是组织内在的。患者输注[1,2-C]乙酸盐和[U-C]谷氨酰胺，并测量分离的人肾和肿瘤线粒体的呼吸作用，揭示 ccRCC 中的电子传递链活性降低，导致氧化减少和增强的还原 TCA 循环标记。然而，ccRCC 转移与原发性 ccRCC 相比，TCA 循环标记出乎意料地增加，表明患者转移过程中存在不同的代谢程序。在小鼠中，刺激肾癌细胞的呼吸或 NADH 循环足以促进转移，而抑制电子传递链复合物 I 可减少转移。这些在人类和小鼠中的发现表明，代谢特性和缺陷在肾癌进展过程中发生演变，并且线粒体功能对转移而不是原始部位的生长具有限制作用。

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2
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Nat Cancer. 2023 Jul;4(7):984-1000. doi: 10.1038/s43018-023-00584-1. Epub 2023 Jun 26.
3
Complex I inhibitor of oxidative phosphorylation in advanced solid tumors and acute myeloid leukemia: phase I trials.
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bioRxiv. 2025 Aug 12:2023.12.02.569652. doi: 10.1101/2023.12.02.569652.
4
Mitochondrial glutathione import enables breast cancer metastasis via integrated stress response signaling.线粒体谷胱甘肽导入通过整合应激反应信号传导促进乳腺癌转移。
Cancer Discov. 2025 Jul 31. doi: 10.1158/2159-8290.CD-24-1556.
5
Conservation and divergence of metabolic phenotypes between patient tumours and matched xenografts.患者肿瘤与其匹配的异种移植瘤之间代谢表型的保守性与差异性。
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