Evidence map›Paper›PMID 41068982›Full record

ArticleCancer & metabolism2025

The integration of single-cell and metabolomics reveals the increase of oxidative phosphorylation during the liver metastasis of colorectal cancer.

Tianyu Liu, Sizheng Sun, Yicheng Huang, Yiming E, Wenyuan Li, Fanggui Xu, Zhengxia Liu, Xiagang Luo, Chen Lu, Chunzhao Yu

Abstract read
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Article in Cancer & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

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5citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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5 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Tianyu Liu *Department of General Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211112, China.
Sizheng Sun *Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
Yicheng HuangDepartment of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
Yiming EDepartment of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
Wenyuan LiDepartment of Anesthesiology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
Fanggui XuDepartment of General Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211112, China.
Zhengxia LiuDepartment of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China.
Xiagang LuoDepartment of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210011, China. jssylxg2003@njmu.edu.cn.
Chen LuDepartment of General Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211112, China. zhongdaluchen@hotmail.com.
Chunzhao YuDepartment of General Surgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211112, China. chunzhaoyu@njmu.edu.cn.

Funding

General Program of Jiangsu Commission of Health No. M2024079General Program of National Natural Science Foundation of China No.82373293Primary Research and Development Plan of Jiangsu Province No. BE2019759Research Project of Jiangsu Commission of Health No. ZD2022063The fifth phase of the "333 Project" scientific research project of Jiangsu Province No. BRA2020091The National Key Research and Development Program of China No. 2018YFE0127300
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) is among the most prevalent malignant tumors, with liver metastasis as the leading cause of mortality. Although metabolic reprogramming is known to play a crucial role in tumor metastasis, our understanding of this process during colorectal cancer liver metastasis (CRLM) remains limited.

methodsA stepwise mouse model of CRC liver metastasis was developed, and metabolomic profiling was performed to verify model stability and identify metabolic changes. Single-cell RNA sequencing (scRNA-seq) was used to assess oxidative phosphorylation (OXPHOS) activity within the metastatic tumor microenvironment (TME). Additionally, spatial transcriptomics (ST) was conducted to elucidate the spatial distribution of metabolic phenotypes within metastatic sites. Finally, in vivo experiments were conducted by administering TGFβ inhibitor (LY2157299) or OXPHOS inhibitor (IACS-010759) to evaluate the potential for liver metastasis, and in vitro, the functions of HCT116 and SW620 cells were assessed through Transwell assays and oxygen consumption rate (OCR) measurements.

resultsMetabolomic profiling revealed heightened tricarboxylic acid (TCA) cycle activity in liver metastases. ScRNA-seq analysis showed increased OXPHOS in metastatic cells, including a highly malignant cell subtype characterized by augmented OXPHOS. Further analysis identified a significant upregulation of OXPHOS associated with TGFβ pathway activation. ST localized this OXPHOS -enriched subtype within metastatic tissue. Both in vivo and in vitro experiments demonstrate that inhibition of TGFβ signaling reduces OXPHOS activity, thereby attenuating the progression of colorectal cancer liver metastasis.

conclusionsThis study identifies OXPHOS upregulation as a key metabolic alteration during CRC liver metastasis, which could be induced by TGFβ signaling pathway. These findings contribute to a refined understanding of CRC metabolic adaptation in liver metastases and may inform therapeutic strategies targeting OXPHOS in advanced CRC.

Indexed as

Colorectal cancerLiver metastasisOxidative phosphorylationTGFβ

Identifiers

PMID41068982
PMCPMC12512483

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