Evidence map›Paper›PMID 33468992›Full record

ArticleOncogenesis2021

PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas.

Changhwan Yoon, Jun Lu, Brendan C Yi, Kevin K Chang, M Celeste Simon, Sandra Ryeom, Sam S Yoon

RetractedOpen access · goldAbstract readRetracted Publication
In one paragraph

Article in Oncogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.1field-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

31 citing papers in PubMed, 70 citations in OpenAlex.

  1. CD4Science advances · 2025
    Article
  2. Article
  3. Retraction: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Down-Regulation of CYP3A4 by the KInternational journal of molecular sciences · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Changhwan YoonDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-8420-9818
Jun LuDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Brendan C YiDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4845-2343
Kevin K ChangDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
M Celeste SimonAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sandra RyeomDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sam S YoonDepartment of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. yoons@mskcc.org.ORCID http://orcid.org/0000-0002-5033-6501
Memorial Sloan Kettering Cancer Center · USCancer Research Institute · USFujian Medical University · CNUniversity of Pennsylvania · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
HIFs and VEGF in sarcoma progression, metastasis, and radiation responseR01CA158301 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SIMON, M. CELESTE, YOON, SAM SUNGHYUN · 2011 to 2021
$4.1M
NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA158301
6 · The paper itself

Abstract

The self-renewal transcription factor Nanog and the phosphoinositide 3-kinase (PI3K)-Akt pathway are known to be essential for maintenance of mesenchymal stem cells. We evaluated their contribution to the maintenance of CD133(+) cancer stem-like cells (CSCs) and spheroid-forming cells in patient-derived cell lines from three human sarcoma subtypes: HT1080 fibrosarcoma, SK-LMS-1 leiomyosarcoma, and DDLS8817 dedifferentiated liposarcoma. Levels of Nanog and activated Akt were significantly higher in sarcoma cells grown as spheroids or sorted for CD133 expression to enrich for CSCs. shRNA knockdown of Nanog decreased spheroid formation 10- to 14-fold, and reversed resistance to both doxorubicin and radiation in vitro and in H1080 flank xenografts. In the HT1080 xenograft model, doxorubicin and Nanog knockdown reduced tumor growth by 34% and 45%, respectively, and the combination reduced tumor growth by 74%. Using a human phospho-kinase antibody array, Akt1/2 signaling, known to regulate Nanog, was found to be highly activated in sarcoma spheroid cells compared with monolayer cells. Pharmacologic inhibition of Akt using LY294002 and Akt1/2 knockdown using shRNA in sarcoma CSCs decreased Nanog expression and spheroid formation and reversed chemotherapy resistance. Akt1/2 inhibition combined with doxorubicin treatment of HT1080 flank xenografts reduced tumor growth by 73%. Finally, in a human sarcoma tumor microarray, expression of CD133, Nanog, and phospho-Akt were 1.8- to 6.8-fold higher in tumor tissue compared with normal tissue. Together, these results indicate that the Akt1/2-Nanog pathway is critical for maintenance of sarcoma CSCs and spheroid-forming cells, supporting further exploration of this pathway as a therapeutic target in sarcoma.

Identifiers

PMID33468992
PMCPMC7815726
OpenAlexW3124641958

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.