文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
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
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
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 @ 2025

丙酸代谢改变导致肿瘤进展和侵袭性增加。

Altered propionate metabolism contributes to tumour progression and aggressiveness.

机构信息

Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.

Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.

出版信息

Nat Metab. 2022 Apr;4(4):435-443. doi: 10.1038/s42255-022-00553-5. Epub 2022 Mar 31.

DOI:10.1038/s42255-022-00553-5
PMID:35361954
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9050834/
Abstract

The alteration of metabolic pathways is a critical strategy for cancer cells to attain the traits necessary for metastasis in disease progression. Here, we find that dysregulation of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells, increasing their metastatic potential. This occurs through the downregulation of methylmalonyl coenzyme A epimerase (MCEE), mediated by an extracellular signal-regulated kinase 2-driven transcription factor Sp1/early growth response protein 1 transcriptional switch driven by metastatic signalling at its promoter level. The loss of MCEE results in reduced propionate-driven anaplerotic flux and intracellular and intratumoral accumulation of methylmalonic acid, a by-product of propionate metabolism that promotes cancer cell invasiveness. Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as an important contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas.

摘要

代谢途径的改变是癌细胞获得疾病进展中转移所需特征的关键策略。在这里，我们发现丙酸盐代谢的失调会在乳腺和肺癌细胞中产生促进侵袭的特征，增加它们的转移潜力。这是通过细胞外信号调节激酶 2 驱动的转录因子 Sp1/早期生长反应蛋白 1 转录开关介导的丙酰辅酶 A 差向异构酶（MCEE）的下调来实现的，该转录开关由转移信号在其启动子水平驱动。MCEE 的缺失导致丙酸盐驱动的补充代谢通量减少，以及甲基丙二酸在细胞内和肿瘤内的积累，甲基丙二酸是丙酸盐代谢的副产物，可促进癌细胞侵袭性。总之，我们提出了一种以前未被描述的丙酸盐代谢失调，它是癌症的一个重要贡献因素，也是转移性癌治疗的一个有价值的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/089f42c3246c/nihms-1781248-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/8922f6ec9b17/nihms-1781248-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/a0d46b13109c/nihms-1781248-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/1739661b225c/nihms-1781248-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/47c070bcc330/nihms-1781248-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/2d7c876aa5a1/nihms-1781248-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/91da574b3f1a/nihms-1781248-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/1f331c80e32e/nihms-1781248-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/b8132e2f8e36/nihms-1781248-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/d9f352b89b96/nihms-1781248-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/089f42c3246c/nihms-1781248-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/8922f6ec9b17/nihms-1781248-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/a0d46b13109c/nihms-1781248-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/1739661b225c/nihms-1781248-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/47c070bcc330/nihms-1781248-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/2d7c876aa5a1/nihms-1781248-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/91da574b3f1a/nihms-1781248-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/1f331c80e32e/nihms-1781248-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/b8132e2f8e36/nihms-1781248-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/d9f352b89b96/nihms-1781248-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0da/9050834/089f42c3246c/nihms-1781248-f0004.jpg

相似文献

[1]
Altered propionate metabolism contributes to tumour progression and aggressiveness.

Nat Metab. 2022-4

[2]
Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes.

Mol Genet Metab. 2020-7

[3]
Age-induced accumulation of methylmalonic acid promotes tumour progression.

Nature. 2020-8-19

[4]
Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism.

Mol Genet Metab. 2006

[5]
Atypical methylmalonic aciduria: frequency of mutations in the methylmalonyl CoA epimerase gene (MCEE).

Hum Mutat. 2007-10

[6]
Homozygous nonsense mutation in the MCEE gene and siRNA suppression of methylmalonyl-CoA epimerase expression: a novel cause of mild methylmalonic aciduria.

Mol Genet Metab. 2006-8

[7]
A homozygous nonsense mutation in the methylmalonyl-CoA epimerase gene (MCEE) results in mild methylmalonic aciduria.

Hum Mutat. 2006-7

[8]
[13C]Valine metabolism in methylmalonicacidemia using nuclear magnetic resonance: propinonate as an obligate intermediate.

Proc Natl Acad Sci U S A. 1975-9

[9]
Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.

Am J Physiol Endocrinol Metab. 2018-7-17

[10]
Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency.

Biochim Biophys Acta Mol Basis Dis. 2019-1-22

引用本文的文献

[1]
Gut microbiota shapes cancer immunotherapy responses.

NPJ Biofilms Microbiomes. 2025-7-25

[2]
Integrated single-cell and bulk RNA sequencing reveals prognostic and immunotherapy-associated myofibroblastic cancer-associated fibroblast subtypes in head and neck squamous cell carcinoma.

Transl Cancer Res. 2025-6-30

[3]
Cancer progression through the lens of age-induced metabolic reprogramming.

Nat Rev Cancer. 2025-7-11

[4]
Identification and prognostic analysis of propionate metabolism-related genes in head and neck squamous cell carcinoma.

Front Oncol. 2025-6-12

[5]
Microbial diagnostic features identified across populations possess potential antitumor properties in breast cancer.

mSystems. 2025-7-22

[6]
Propionate metabolism-related genes demonstrate the potential to serve as prognostic and immunotherapeutic markers in osteosarcoma.

Oncol Lett. 2025-6-10

[7]
Machine learning identifies SRD5A3 as a propionate-related prognostic biomarker in triple-negative breast cancer.

Sci Rep. 2025-5-29

[8]
Revealing propionate metabolism-related genes in glioblastoma and investigating their underlying mechanisms.

Front Oncol. 2025-4-17

[9]
Mannose Inhibits NSCLC Growth and Inflammatory Microenvironment by Regulating Gut Microbiota and Targeting OGT/hnRNP R/JUN/IL-8 Axis.

Int J Biol Sci. 2025-1-27

[10]
Exploring the causal associations of the gut microbiota and plasma metabolites with ovarian cancer: an approach of mendelian randomization analysis combined with network pharmacology and molecular docking.

J Ovarian Res. 2025-2-13

本文引用的文献

[1]
In Vivo Evidence for Serine Biosynthesis-Defined Sensitivity of Lung Metastasis, but Not of Primary Breast Tumors, to mTORC1 Inhibition.

Mol Cell. 2021-1-21

[2]
Age-induced accumulation of methylmalonic acid promotes tumour progression.

Nature. 2020-8-19

[3]
Limited Environmental Serine and Glycine Confer Brain Metastasis Sensitivity to PHGDH Inhibition.

Cancer Discov. 2020-9

[4]
Dynamic Incorporation of Histone H3 Variants into Chromatin Is Essential for Acquisition of Aggressive Traits and Metastatic Colonization.

Cancer Cell. 2019-9-26

[5]
Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples.

Sci Rep. 2019-9-16

[6]
Are 90% of deaths from cancer caused by metastases?

Cancer Med. 2019-8-8

[7]
ERK2 regulates epithelial-to-mesenchymal plasticity through DOCK10-dependent Rac1/FoxO1 activation.

Proc Natl Acad Sci U S A. 2019-2-6

[8]
Measuring In Vivo Tissue Metabolism Using C Glucose Infusions in Mice.

Methods Mol Biol. 2019

[9]
Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass.

Science. 2017-11-17

[10]
Fundamentals of cancer metabolism.

Sci Adv. 2016-5-27

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索