Evidence map›Paper›PMID 30286779›Full record

ArticleJournal of experimental & clinical cancer research : CR2018

Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells.

Dongqing Zuo, Kristen L Shogren, Jie Zang, Donna E Jewison, Brian E Waletzki, Alan L Miller, Scott H Okuno, Zhengdong Cai, Michael J Yaszemski, Avudaiappan Maran

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.7field-weighted citation impact, top 7% 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

42 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Oncology reports · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Possible Role of IL-6R/STAT3/MiRNA-34a Feedback Loop in Osteosarcoma.Asian Pacific journal of cancer prevention : APJCP · 2023
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. PROTACs in gastrointestinal cancers.Molecular therapy oncolytics · 2022
    Review
  20. Article
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

10 authors at 4 institutions in 2 countries.

Dongqing ZuoDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Kristen L ShogrenDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Jie ZangMusculoskeletal Tumor Center, People's Hospital, Peking University, Beijing, 100044, China.
Donna E JewisonDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Brian E WaletzkiDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Alan L Miller
Scott H OkunoDivision of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Zhengdong CaiDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Michael J YaszemskiDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA.
Avudaiappan MaranDepartment of Orthopedic Surgery, 2-69 Medical Sciences, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. maran.avudai@mayo.edu.ORCID http://orcid.org/0000-0003-3138-3318
Mayo Clinic · USMayo Clinic in Arizona · USPeking University · CNShanghai Jiao Tong University · CN

Funding

Mayo Clinic Rice University Dental, Oral and Craniofacial Tissue Regeneration Consortium Resource CenterR34DE025593 · NIDCR · MAYO CLINIC ROCHESTER · PI MIKOS, ANTONIOS G., YASZEMSKI, MICHAEL J · 2015 to 2015
$211k
Foundation for the National Institutes of Health R34 grant DE025593National Natural Science Foundation of China 81802985NIDCR NIH HHS R34 DE025593
6 · The paper itself

Abstract

backgroundOsteosarcoma is the most common bone cancer. Despite advances, molecular mechanisms associated with osteosarcoma have not been fully understood. Hence, an effective treatment for osteosarcoma has yet to be developed. Even though signal transducer and activator of transcription3 (STAT3) has been implicated, its role in pathogenesis of osteosarcoma is not fully determined. In this study, we investigated the antitumor effect of napabucasin (NP) (BBI608), an inhibitor of STAT3 on osteosarcoma in vitro and in vivo and studied the underlying molecular mechanism.

methodsCell viability, colony formation, apoptosis, tumor growth and metastasis assays were performed to examine the effect of NP on osteosarcoma in vitro and in vivo. Real-time RT-PCR, western analysis, immunofluorescence and reporter assays were used to monitor the expression and activity of proteins and underlying molecular pathways. Protein synthesis, co-immunoprecipitation and CAP binding assays were carried out to understand NP-mediated mechanism of actions in osteosarcoma cells.

resultsOur results show that NP treatment decreases cell viability and induces apoptosis in several osteosarcoma cell lines. NP treatment suppresses both expression and phosphorylation of STAT3 in addition to blocking STAT3-mediated transcription and downstream target proteins in osteosarcoma cells. Furthermore, NP inhibits protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E-binding protein 1 (4E-BP1). NP also inhibits the progression of osteosarcoma tumors and metastasis in vivo in an orthotopic tibial model of osteosarcoma.

conclusionsTaken together, our investigation reveals that NP acts through a novel mechanism and inhibits osteosarcoma growth and metastasis, and could be investigated clinically for treating osteosarcoma patients alone or in combination with other drugs.

Indexed as

AnimalsApoptosisBenzofuransBone NeoplasmsCell Line, TumorFemaleHumansMiceMice, Inbred BALB CMice, NudeNaphthoquinonesNeoplasm MetastasisOsteosarcomaProtein Synthesis InhibitorsRandom AllocationSTAT3 Transcription FactorBenzofuransnapabucasinNaphthoquinonesProtein Synthesis InhibitorsSTAT3 protein, humanSTAT3 Transcription Factor4EBP-1ApoptosiseIF4ENapabucasinOsteosarcomaProtein synthesis

Identifiers

PMID30286779
PMCPMC6172747
OpenAlexW2895652773

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.