Evidence map›Paper›PMID 31196164›Full record

ArticleStem cell research & therapy2019

Elevated level of mitochondrial reactive oxygen species via fatty acid β-oxidation in cancer stem cells promotes cancer metastasis by inducing epithelial-mesenchymal transition.

Caihua Wang, Liming Shao, Chi Pan, Jun Ye, Zonghui Ding, Jia Wu, Qin Du, Yuezhong Ren, Chunpeng Zhu

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 120 citations in OpenAlex.

  1. Functional Role of COP1 Gene in Hepatocellular Carcinoma Lipid Metabolism and Stemness.Genes to cells : devoted to molecular & cellular mechanisms · 2026
    Article
  2. Article
  3. The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026
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  17. Mitochondrial Reactive Oxygen Species (mROS) Generation and Cancer:International journal of nanomedicine · 2025
    Review
  18. Review
  19. Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Caihua WangDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China.
Liming ShaoDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China.
Chi PanDepartment of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
Jun YeDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China.
Zonghui DingDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Arizona, AZ, 85259, USA.
Jia WuDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China.
Qin DuDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China.
Yuezhong RenDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. renyuez@zju.edu.cn.
Chunpeng ZhuDepartment of Gastroenterology, The Second Affiliated Hospital, ZhejiangUniversity School of Medicine, Hangzhou, 310009, China. zhuchunpeng@zju.edu.cn.ORCID 0000-0003-4861-985X
Second Affiliated Hospital of Zhejiang University · CNMayo Clinic in Arizona · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms.

methodsFour different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis.

resultsTumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid β-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients.

conclusionsOur findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid β-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells.

Indexed as

AnimalsCell Line, TumorEpithelial-Mesenchymal TransitionFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHCT116 CellsHT29 CellsHumansMiceMice, Inbred BALB CMicroscopy, Electron, TransmissionMitochondriaNeoplasmsNeoplastic Stem CellsOxidation-ReductionReactive Oxygen SpeciesCancer metastasisCancer stem cellsEpithelial-mesenchymal transitionMitochondriaROSTumor sphere

Identifiers

PMID31196164
PMCPMC6567550
OpenAlexW2951265455

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.