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琥珀酸等致癌代谢物通过激活 STAT3 促进结直肠癌的远处转移及其潜在机制。

Effect and potential mechanism of oncometabolite succinate promotes distant metastasis of colorectal cancer by activating STAT3.

机构信息

Department of Gastroenterology, Gui Zhou Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guiyang, China.

Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.

出版信息

BMC Gastroenterol. 2024 Mar 14;24(1):106. doi: 10.1186/s12876-024-03195-x.

DOI:10.1186/s12876-024-03195-x
PMID:38486162
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10938789/
Abstract

To investigate the effect of Oncometabolite succinate on colorectal cancer migration and invasion and to initially explore the underlying mechanism.Succinate acid detection kit detected the succinate content in tissues. The growth of colorectal cancer cells was measured by cck-8 assay, wound-healing migration assay and transwell migration and invasion assays, and then explored the level of epithelial-mesenchymal transition (EMT) and STAT3/ p-STAT3 expression by western blot analysis and quantitative real-time PCR for mRNA expression. We found that succinate levels were significantly higher in carcinoma tissues than paracancerous tissues. After succinate treatment, the colorectal cancer cell lines SW480 and HCT116 had enhanced migration and invasion, the expression of biomarkers of EMT was promoted, and significantly increased phosphorylation of STAT3. In vivo experiments also showed that succinate can increase p-STAT3 expression, promote the EMT process, and promote the distant metastasis of colorectal cancer in mice.Succinate promotes EMT through the activation of the transcription factor STAT3, thus promoting the migration and invasion of colorectal cancer.

摘要

为了研究代谢物琥珀酸对结直肠癌迁移和侵袭的影响，并初步探讨其潜在机制。使用琥珀酸检测试剂盒检测组织中的琥珀酸含量。通过 CCK-8 assay、划痕愈合迁移实验和 Transwell 迁移和侵袭实验测量结直肠癌细胞的生长，然后通过 Western blot 分析和定量实时 PCR 检测上皮-间充质转化 (EMT) 和 STAT3/p-STAT3 表达水平，以探讨其机制。我们发现，癌组织中的琥珀酸水平明显高于癌旁组织。琥珀酸处理后，结直肠癌细胞系 SW480 和 HCT116 的迁移和侵袭能力增强，EMT 标志物的表达得到促进，STAT3 的磷酸化水平显著升高。体内实验也表明，琥珀酸可以增加 p-STAT3 的表达，促进 EMT 过程，并促进结直肠癌在小鼠中的远处转移。琥珀酸通过激活转录因子 STAT3 促进 EMT，从而促进结直肠癌细胞的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/aa29231a23cc/12876_2024_3195_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/322ffe08031b/12876_2024_3195_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/6812bccc79e6/12876_2024_3195_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/ccffe0a50c65/12876_2024_3195_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/073439ef9cf5/12876_2024_3195_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/aa29231a23cc/12876_2024_3195_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/322ffe08031b/12876_2024_3195_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/6812bccc79e6/12876_2024_3195_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/ccffe0a50c65/12876_2024_3195_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/073439ef9cf5/12876_2024_3195_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f61b/10938789/aa29231a23cc/12876_2024_3195_Fig5_HTML.jpg

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引用本文的文献

[1]
TCA cycle-derived oncometabolites in cancer and the immune microenvironment.

J Biomed Sci. 2025-9-10

[2]
Gut microbiota and metabolome signatures in obese and normal-weight patients with colorectal tumors.

iScience. 2025-3-13

[3]
Identification of Salivary Biomarkers in Colorectal Cancer by Integrating Olink Proteomics and Metabolomics.

J Proteome Res. 2025-5-2

[4]
Adenosine diphosphate stimulates VEGF-independent choroidal endothelial cell proliferation: A potential escape from anti-VEGF therapy.

Proc Natl Acad Sci U S A. 2025-1-28

[5]
Correction: Effect and potential mechanism of oncometabolite succinate promotes distant metastasis of colorectal cancer by activating STAT3.

BMC Gastroenterol. 2024-11-5

[6]
Oncometabolites at the crossroads of genetic, epigenetic and ecological alterations in cancer.

Cell Death Differ. 2024-12

本文引用的文献

[1]
Cancer-derived extracellular succinate: a driver of cancer metastasis.

J Biomed Sci. 2022-11-7

[2]
STAT3-EMT axis in tumors: Modulation of cancer metastasis, stemness and therapy response.

Pharmacol Res. 2022-8

[3]
The Role of Succinic Acid Metabolism in Ovarian Cancer.

Front Oncol. 2021-11-2

[4]
Cancer metabolism: looking forward.

Nat Rev Cancer. 2021-10

[5]
Targeting key transcriptional factor STAT3 in colorectal cancer.

Mol Cell Biochem. 2021-9

[6]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

[7]
STAT3 Mediates the Differential Effects of Oncostatin M and TNFα on RA Synovial Fibroblast and Endothelial Cell Function.

Front Immunol. 2019-8-28

[8]
Inflammation and Cancer: Triggers, Mechanisms, and Consequences.

Immunity. 2019-7-16

[9]
Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT.

Mol Cancer. 2019-3-13

[10]
EMT Transition States during Tumor Progression and Metastasis.

Trends Cell Biol. 2018-12-26

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