Evidence map›Paper›PMID 31370822›Full record

ArticleBMC cancer2019

Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target.

Xiao-Lu Ma, Yun-Fan Sun, Bei-Li Wang, Min-Na Shen, Yan Zhou, Jian-Wen Chen, Bo Hu, Zi-Jun Gong, Xin Zhang, Ya Cao and 5 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
8.0field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
  2. Review
  3. The metabolic profiles of cancer stem cells.Stem cell research & therapy · 2026
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  9. Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024
    Review
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  11. Article
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  13. Review
  14. Review
  15. Combined Inhibition ofInternational journal of molecular sciences · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

7 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

15 authors at 4 institutions in 1 country.

Xiao-Lu MaDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Yun-Fan SunDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Bei-Li WangDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Min-Na ShenDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Yan ZhouDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Jian-Wen ChenDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Bo HuDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Zi-Jun GongDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Xin ZhangDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Ya CaoCancer Research Institute, Xiangya School of Medicine, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410078, China.
Bai-Shen PanDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Jian ZhouDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Jia FanDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Wei GuoDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. guo.wei@zs-hospital.sh.cn.
Xin-Rong YangDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 136 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China. yang.xinrong@zs-hospital.sh.cn.
Fudan University · CNZhongshan Hospital · CNCentral South University · CNThe First Affiliated Hospital, Sun Yat-sen University · CN

Funding

Selectively targeting delta opioid receptor subtypes to control drinking behaviorR01AA020401 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WHISTLER, JENNIFER L · 2011 to 2015
$1.8M
NIAAA NIH HHS R01 AA020401
6 · The paper itself

Abstract

backgroundsThe role of sphere-forming culture in enriching subpopulations with stem-cell properties in hepatocellular carcinoma (HCC) is unclear. The present study investigates its value in enriching cancer stem cells (CSCs) subpopulations and the mechanism by which HCC CSCs are maintained.

methodsHCC cell lines and fresh primary tumor cells were cultured in serum-free and ultra-low attachment conditions to allow formation of HCC spheres. In vitro and in vivo experiments were performed to evaluate CSC characteristics. Expression levels of CSC-related genes were assessed by qRT-PCR and the correlation between sphere formation and clinical characteristics was investigated. Finally, gene expression profiling was performed to explore the molecular mechanism underlying HCC CSC maintenance.

resultsWe found that both cell lines and primary tumor cells formed spheres. HCC spheres possessed the capacity for self-renewal, proliferation, drug resistance, and contained different subpopulations of CSCs. Of interest, 500 sphere-forming Huh7 cells or 200 primary tumor cells could generate tumors in immunodeficient animals. Sphere formation correlated with size, multiple tumors, satellite lesions, and advanced stage. Further investigation identified that the PPARα-SCD1 axis plays an important role in maintenance of the CSC properties of HCC sphere cells by promoting nuclear accumulation of β-Catenin. Inhibition of SCD1 interfered with sphere formation, down-regulated expression of CSC-related markers, and reduced β-Catenin nuclear accumulation.

conclusionsSphere-forming culture can effectively enrich subpopulations with stem-cell properties, which are maintained through activation of the PPARα-SCD1 axis. Therefore, we suggest that targeting the SCD1-related CSC machinery might provide a novel insight into HCC treatment.

Indexed as

AnimalsCarcinoma, HepatocellularCell Line, TumorCell ProliferationCell Self RenewalDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHumansLiver NeoplasmsMiceMice, SCIDMolecular Targeted TherapyNeoplastic Stem CellsPPAR alphaSignal TransductionSpheroids, CellularPPAR alphaSCD1 protein, humanStearoyl-CoA DesaturaseCancer stem cellHepatocellular carcinomaSphere-forming assayStearoyl-CoA desaturase 1

Identifiers

PMID31370822
PMCPMC6676608
OpenAlexW2966556043

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.