Evidence mapPaperPMID 31446059Full record

ArticleGastroenterology2019

New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation.

Justin L Tan, Feng Li, Joanna Z Yeo, Kol Jia Yong, Mahmoud A Bassal, Guo Hao Ng, May Yin Lee, Chung Yan Leong, Hong Kee Tan, Chan-Shuo Wu and 27 more

Open access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
2.4field-weighted citation impact, top 10% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. FMolecular biology reports · 2023
    Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Frontiers in immunology · 2025
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 8 institutions in 4 countries.

Justin L TanCancer Science Institute of Singapore, National University of Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Feng LiCancer Science Institute of Singapore, National University of Singapore, Singapore.
Joanna Z YeoCancer Science Institute of Singapore, National University of Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Kol Jia YongCancer Science Institute of Singapore, National University of Singapore, Singapore.
Mahmoud A BassalCancer Science Institute of Singapore, National University of Singapore, Singapore; Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts.
Guo Hao NgGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
May Yin LeeGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Chung Yan LeongBioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Hong Kee TanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Chan-Shuo WuCancer Science Institute of Singapore, National University of Singapore, Singapore.
Bee Hui LiuCancer Science Institute of Singapore, National University of Singapore, Singapore.
Tim H ChanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Zi Hui TanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Yun Shen ChanGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Siyu WangGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Zhi Han LimGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Tan Boon TohCancer Science Institute of Singapore, National University of Singapore, Singapore.
Lissa HooiCancer Science Institute of Singapore, National University of Singapore, Singapore.
Kia Ngee LowBioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Siming MaGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Nikki R KongDepartment of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Alicia J SteinDepartment of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Yue WuDepartment of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Matan T ThangaveluGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Atsushi SuzukiDivision of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Giridharan PeriyasamyGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
John M AsaraDepartment of Medicine, Division of Signal Transduction, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Yock Young DanCancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Health System, Singapore.
Glenn K BonneyDepartment of Hepatobiliary, Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore; National University Centre for Organ Transplantation, National University Hospital, Singapore.
Edward K ChowCancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Guo-Dong LuCancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, China; Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education of China, Nanning, China.
Huck Hui NgGenome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
Yoganathan KanagasundaramBioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Siew Bee NgBioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
Wai Leong TamCancer Science Institute of Singapore, National University of Singapore, Singapore; Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; School of Biological Sciences, Nanyang Technological University, Singapore.
Daniel G TenenCancer Science Institute of Singapore, National University of Singapore, Singapore; Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts. Electronic address: daniel.tenen@nus.edu.sg.
Li ChaiDepartment of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Agency for Science, Technology and Research · SGNational University of Singapore · SGBrigham and Women's Hospital · USHarvard University · USBeth Israel Deaconess Medical Center · USGuangxi Medical University · CNKyushu University · JPNational University Hospital · SG

Funding

Project 4 - Mechanisms of establishing clonal dominanceP01HL131477 · MASSACHUSETTS GENERAL HOSPITAL · 2025 to 2025
$2.5M
NCI NIH HHS R35 CA197697NHLBI NIH HHS P01 HL095489NHLBI NIH HHS P01 HL131477
6 · The paper itself

Abstract

BACKGROUND &

aimsSome oncogenes encode transcription factors, but few drugs have been successfully developed to block their activity specifically in cancer cells. The transcription factor SALL4 is aberrantly expressed in solid tumor and leukemia cells. We developed a screen to identify compounds that reduce the viability of liver cancer cells that express high levels of SALL4, and we investigated their mechanisms.

methodsWe developed a stringent high-throughput screening platform comprising unmodified SNU-387 and SNU-398 liver cancer cell lines and SNU-387 cell lines engineered to express low and high levels of SALL4. We screened 1597 pharmacologically active small molecules and 21,575 natural product extracts from plant, bacteria, and fungal sources for those that selectively reduce the viability of cells with high levels of SALL4 (SALL4

resultsOur screening identified 1 small molecule (PI-103) and 4 natural compound analogues (oligomycin, efrapeptin, antimycin, and leucinostatin) that selectively reduced viability of SALL4

conclusionsIn a screening for compounds that reduce the viability of cells that express high levels of the transcription factor SALL4, we identified inhibitors of oxidative phosphorylation, which slowed the growth of xenograft tumors from SALL4

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHigh-Throughput Screening AssaysHumansLiver NeoplasmsMaleMiceOxidative PhosphorylationTranscription FactorsUp-RegulationAntineoplastic AgentsSALL4 protein, humanTranscription FactorsChemical-Genetic ScreenHCCMetabolic VulnerabilityMetabolism

Identifiers

PMID31446059
PMCPMC7309153
OpenAlexW2969431868

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.