Evidence map›Paper›PMID 28459464›Full record

ArticleOncogene2017

Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells.

E Raja, A Komuro, R Tanabe, S Sakai, Y Ino, N Saito, T Todo, M Morikawa, H Aburatani, D Koinuma and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. The TGF-β Family in Glioblastoma.International journal of molecular sciences · 2024
    Review
  7. Article
  8. BMP signaling in cancer stemness and differentiation.Cell regeneration (London, England) · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  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

12 authors at 1 institution in 1 country.

E RajaDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
A KomuroDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
R TanabeDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
S SakaiDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Y InoDivision of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
N SaitoDepartment of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
T TodoDivision of Innovative Cancer Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
M MorikawaDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
H AburataniGenome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
D KoinumaDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
C IwataDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
K MiyazonoDepartment of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
The University of Tokyo · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.

Indexed as

Activin Receptors, Type IAnimalsApoptosisBone Morphogenetic ProteinsBrain NeoplasmsCell DifferentiationFemaleGliomaHEK293 CellsHeterograftsHomeodomain ProteinsHumansMiceMice, Inbred BALB CMice, NudeNeoplastic Stem CellsActivin Receptors, Type IACVR1 protein, humanBone Morphogenetic ProteinsDLX2 protein, humanHomeodomain ProteinsTranscription FactorsValproic Acid

Identifiers

PMID28459464
OpenAlexW2611143614

What OpenQuestion holds

Textmetadata
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.