Evidence map›Paper›PMID 30403311›Full record

ArticleBrain pathology (Zurich, Switzerland)2019

Regulation of glioma cell invasion by 3q26 gene products PIK3CA, SOX2 and OPA1.

Thorsten Schaefer, Archana Ramadoss, Severina Leu, Lionel Tintignac, Cristobal Tostado, Andrea Bink, Christoph Schürch, Joëlle Müller, Jonas Schärer, Giusi Moffa and 12 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain pathology (Zurich, Switzerland), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 19% 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, 17 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

22 authors at 1 institution in 1 country.

Thorsten SchaeferStem Cells and Hematopoiesis Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Archana RamadossLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Severina LeuNeurosurgery Clinic, University Hospital and University of Basel, Basel, Switzerland.
Lionel TintignacNeuromuscular Research Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Cristobal TostadoLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Andrea BinkDepartment of Neuroradiology, University Hospital and University of Basel, Basel, Switzerland.ORCID 0000-0002-2163-3400
Christoph SchürchStem Cells and Hematopoiesis Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Joëlle MüllerStem Cells and Hematopoiesis Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Jonas SchärerStem Cells and Hematopoiesis Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Giusi MoffaBasel Institute for Clinical Epidemiology and Biostatistics, University Hospital and University of Basel, Basel, Switzerland.ORCID 0000-0002-2739-0454
Philippe DemouginLife Sciences Training Facility, University of Basel, Basel, Switzerland.
Suzette MoesProteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland.
Christoph StippichDepartment of Neuroradiology, University Hospital and University of Basel, Basel, Switzerland.
Simona FalboLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Heike NeddersenNeurosurgery Clinic, University Hospital and University of Basel, Basel, Switzerland.
Heiner BucherBasel Institute for Clinical Epidemiology and Biostatistics, University Hospital and University of Basel, Basel, Switzerland.
Stephan FrankDivision of Neuropathology, University Hospital and University of Basel, Basel, Switzerland.
Paul JenöProteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland.
Claudia LengerkeStem Cells and Hematopoiesis Laboratory, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Marie-Françoise RitzLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Luigi MarianiLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Jean-Louis BoulayLaboratory of Brain Tumor Biology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.ORCID 0000-0002-1401-7159
University of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diffuse gliomas progress by invading neighboring brain tissue to promote postoperative relapse. Transcription factor SOX2 is highly expressed in invasive gliomas and maps to chromosome region 3q26 together with the genes for PI3K/AKT signaling activator PIK3CA and effector molecules of mitochondria fusion and cell invasion, MFN1 and OPA1. Gene copy number analysis at 3q26 from 129 glioma patient biopsies revealed mutually exclusive SOX2 amplifications (26%) and OPA1 losses (19%). Both forced SOX2 expression and OPA1 inactivation increased LN319 glioma cell invasion in vitro and promoted cell dispersion in vivo in xenotransplanted D. rerio embryos. While PI3 kinase activity sustained SOX2 expression, pharmacological PI3K/AKT pathway inhibition decreased invasion and resulted in SOX2 nucleus-to-cytoplasm translocation in an mTORC1-independent manner. Chromatin immunoprecipitation and luciferase reporter gene assays together demonstrated that SOX2 trans-activates PIK3CA and OPA1. Thus, SOX2 activates PI3K/AKT signaling in a positive feedback loop, while OPA1 deletion is interpreted to counteract OPA1 trans-activation. Remarkably, neuroimaging of human gliomas with high SOX2 or low OPA1 genomic imbalances revealed significantly larger necrotic tumor zone volumes, corresponding to higher invasive capacities of tumors, while autologous necrotic cells are capable of inducing higher invasion in SOX2 overexpressing or OPA1 knocked-down relative to parental LN319. We thus propose necrosis volume as a surrogate marker for the assessment of glioma invasive potential. Whereas glioma invasion is activated by a PI3K/AKT-SOX2 loop, it is reduced by a cryptic invasion suppressor SOX2-OPA1 pathway. Thus, PI3K/AKT-SOX2 and mitochondria fission represent connected signaling networks regulating glioma invasion.

Indexed as

Chromosomes, Human, Pair 3Cell Line, TumorCell MovementCell ProliferationClass I Phosphatidylinositol 3-KinasesDNA Copy Number VariationsGliomaGTP PhosphohydrolasesHEK293 CellsHumansNecrosisNeoplasm InvasivenessNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasesPhosphorylationProto-Oncogene Proteins c-aktClass I Phosphatidylinositol 3-KinasesGTP PhosphohydrolasesOPA1 protein, humanPhosphatidylinositol 3-KinasesPIK3CA protein, humanProto-Oncogene Proteins c-aktSOX2 protein, humanSOXB1 Transcription Factors3q26cell invasionGliomaneuroimagingtumor necrosis

Identifiers

PMID30403311
PMCPMC8028334
OpenAlexW2900321918

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.