Evidence map›Paper›PMID 26997645›Full record

ArticleStem cell reports2016

An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.

Shingo Komura, Katsunori Semi, Fumiaki Itakura, Hirofumi Shibata, Takatoshi Ohno, Akitsu Hotta, Knut Woltjen, Takuya Yamamoto, Haruhiko Akiyama, Yasuhiro Yamada

Open access · goldAbstract read
In one paragraph

Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

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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 2 institutions in 1 country.

Shingo KomuraLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Katsunori SemiLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507, Japan.
Fumiaki ItakuraLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hirofumi ShibataLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Takatoshi OhnoDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Akitsu HottaLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507, Japan.
Knut WoltjenLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Hakubi Center for Advanced Research, Kyoto University, Kyoto 606-8501, Japan.
Takuya YamamotoLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507, Japan; AMED-CREST, AMED 1-7-1 Otemach, Chiyodaku, Tokyo 100-0004, Japan.
Haruhiko AkiyamaDepartment of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
Yasuhiro YamadaLaboratory of Stem Cell Oncology, Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8507, Japan. Electronic address: y-yamada@cira.kyoto-u.ac.jp.
Kyoto University · JPGifu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

EWS-FLI1, a multi-functional fusion oncogene, is exclusively detected in Ewing sarcomas. However, previous studies reported that rare varieties of osteosarcomas also harbor EWS-ETS family fusion. Here, using the doxycycline-inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also show that sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited an impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrate that EWS-FLI1 contributed to secondary sarcoma development from the sarcoma iPSCs after osteogenic differentiation. These findings demonstrate that modulating cellular differentiation is a fundamental principle of EWS-FLI1-induced osteosarcoma development. This in vitro cancer model using sarcoma iPSCs should provide a unique platform for dissecting relationships between the cancer genome and cellular differentiation.

Indexed as

AnimalsBlotting, WesternBone NeoplasmsCarcinogenesisCell DifferentiationCell LineageCell Line, TumorCell Transformation, NeoplasticGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInduced Pluripotent Stem CellsMice, Inbred BALB CMice, Inbred C57BLMice, NudeMice, SCIDEWS-FLI fusion proteinOncogene Proteins, FusionProto-Oncogene Protein c-fli-1RNA-Binding Protein EWS

Identifiers

PMID26997645
PMCPMC4834047
OpenAlexW2299731954

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.