Evidence map›Paper›PMID 35562901›Full record

ArticleInternational journal of molecular sciences2022

High SOX9 Maintains Glioma Stem Cell Activity through a Regulatory Loop Involving STAT3 and PML.

Paula Aldaz, Natalia Martín-Martín, Ander Saenz-Antoñanzas, Estefania Carrasco-Garcia, María Álvarez-Satta, Alejandro Elúa-Pinin, Steven M Pollard, Charles H Lawrie, Manuel Moreno-Valladares, Nicolás Samprón and 4 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.9field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

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  8. LncRNA-Mediated TPI1 and PKM2 Promote Self-Renewal and Chemoresistance in GBM.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
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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

14 authors at 8 institutions in 3 countries.

Paula AldazGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Natalia Martín-MartínCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain.
Ander Saenz-AntoñanzasGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Estefania Carrasco-GarciaGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
María Álvarez-SattaGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Alejandro Elúa-PininDonostia University Hospital, 20014 San Sebastian, Spain.
Steven M PollardCentre for Regenerative Medicine & Edinburgh Cancer Research UK Centre, Institute for Regeneration and Repair, Edinburgh EH16 4UU, UK.
Charles H LawrieGroup of Molecular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.ORCID 0000-0002-8882-1131
Manuel Moreno-ValladaresGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Nicolás SamprónGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Jürgen HenchInstitute of Pathology, University Hospital Basel, 48009 Basel, Switzerland.
Robin Lovell-BadgeThe Francis Crick Institute, London NW1 1AT, UK.ORCID 0000-0001-9364-4179
Arkaitz CarracedoCenter for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain.ORCID 0000-0001-5957-1260
Ander MatheuGroup of Cellular Oncology, Biodonostia Health Research Institute, 20014 San Sebastian, Spain.
Biogipuzkoa Health Research Institute · ESIkerbasque · ESCIC bioGUNE · ESEdinburgh Cancer Research · GBInstituto de Salud Carlos III · ESThe Francis Crick Institute · GBUniversity Hospital of Basel · CHUniversity of the Basque Country · ES

Funding

Instituto de Salud Carlos III PI16/01580
6 · The paper itself

Abstract

Glioma stem cells (GSCs) are critical targets for glioma therapy. SOX9 is a transcription factor with critical roles during neurodevelopment, particularly within neural stem cells. Previous studies showed that high levels of SOX9 are associated with poor glioma patient survival. SOX9 knockdown impairs GSCs proliferation, confirming its potential as a target for glioma therapy. In this study, we characterized the function of SOX9 directly in patient-derived glioma stem cells. Notably, transcriptome analysis of GSCs with SOX9 knockdown revealed STAT3 and PML as downstream targets. Functional studies demonstrated that SOX9, STAT3, and PML form a regulatory loop that is key for GSC activity and self-renewal. Analysis of glioma clinical biopsies confirmed a positive correlation between SOX9/STAT3/PML and poor patient survival among the cases with the highest SOX9 expression levels. Importantly, direct STAT3 or PML inhibitors reduced the expression of SOX9, STAT3, and PML proteins, which significantly reduced GSCs tumorigenicity. In summary, our study reveals a novel role for SOX9 upstream of STAT3, as a GSC pathway regulator, and presents pharmacological inhibitors of the signaling cascade.

Indexed as

Brain NeoplasmsGlioblastomaGliomaCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansNeoplastic Stem CellsSOX9 Transcription FactorSTAT3 Transcription FactorSOX9 protein, humanSOX9 Transcription FactorSTAT3 protein, humanSTAT3 Transcription Factorglioblastomaglioma stem cellpharmacological inhibitionPMLSOX9STAT3therapytranscriptome

Identifiers

PMID35562901
PMCPMC9104987
OpenAlexW4224280644

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.