Evidence map›Paper›PMID 38674001›Full record

ArticleInternational journal of molecular sciences2024

The

Elisabet Ampudia-Mesias, Charles S Cameron, Eunjae Yoo, Marcus Kelly, Sarah M Anderson, Riley Manning, Juan E Abrahante Lloréns, Christopher L Moertel, Hyungshin Yim, David J Odde and 2 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Medulloblastoma: biology and immunotherapy.Frontiers in immunology · 2025
    Review
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 3 institutions in 2 countries.

Elisabet Ampudia-MesiasDivision of Hematology and Oncology, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA.
Charles S CameronDivision of Hematology and Oncology, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA.
Eunjae YooDivision of Hematology and Oncology, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA.
Marcus KellyDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0002-4203-4853
Sarah M AndersonDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Riley ManningDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Juan E Abrahante LlorénsUniversity of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Christopher L MoertelDivision of Hematology and Oncology, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA.ORCID 0000-0002-5474-588X
Hyungshin YimDepartment of Pharmacy, Institute of Pharmaceutical Science and Technology, College of Pharmacy, Hanyang University, Ansan 15588, Gyeonggi-do, Republic of Korea.ORCID 0000-0001-7945-3472
David J OddeDepartment of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.ORCID 0000-0001-7731-2799
Nurten SaydamExoMed Diagnostic, Minneapolis, MN 55404, USA.
Okay SaydamDivision of Hematology and Oncology, Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA.
University of Minnesota · USUniversity of Minnesota Medical Center · USHanyang University · KR

Funding

Project 2: Cell Migration in Mechanically Complex MicroenvironmentsU54CA210190 · NCI · UNIVERSITY OF MINNESOTA · PI ODDE, DAVID J. · 2016 to 2020
$10.0M
Project 3P01CA254849 · NCI · UNIVERSITY OF MINNESOTA · PI LARGAESPADA, DAVID ANDREW, MASOPUST, DAVID · 2021 to 2025
$9.4M
TECH CoreU54CA268069 · NCI · UNIVERSITY OF MINNESOTA · PI Kevin William Eliceiri, Paolo Provenzano · 2022 to 2026
$8.2M
NCI NIH HHS P01 CA254849NCI NIH HHS U54 CA210190NCI NIH HHS U54 CA268069
6 · The paper itself

Abstract

Medulloblastoma (MB) encompasses diverse subgroups, and leptomeningeal disease/metastasis (LMD) plays a substantial role in associated fatalities. Despite extensive exploration of canonical genes in MB, the molecular mechanisms underlying LMD and the involvement of the orthodenticle homeobox 2 (OTX2) gene, a key driver in aggressive MB Group 3, remain insufficiently understood. Recognizing OTX2's pivotal role, we investigated its potential as a catalyst for aggressive cellular behaviors, including migration, invasion, and metastasis. OTX2 overexpression heightened cell growth, motility, and polarization in Group 3 MB cells. Orthotopic implantation of OTX2-overexpressing cells in mice led to reduced median survival, accompanied by the development of spinal cord and brain metastases. Mechanistically, OTX2 acted as a transcriptional activator of the Mechanistic Target of Rapamycin (mTOR) gene's promoter and the mTORC2 signaling pathway, correlating with upregulated downstream genes that orchestrate cell motility and migration. Knockdown of mTOR mRNA mitigated OTX2-mediated enhancements in cell motility and polarization. Analysis of human MB tumor samples (N = 952) revealed a positive correlation between OTX2 and mTOR mRNA expression, emphasizing the clinical significance of OTX2's role in the mTORC2 pathway. Our results reveal that OTX2 governs the mTORC2 signaling pathway, instigating LMD in Group 3 MBs and offering insights into potential therapeutic avenues through mTORC2 inhibition.

Indexed as

Gene Expression Regulation, NeoplasticMechanistic Target of Rapamycin Complex 2MedulloblastomaMeningeal NeoplasmsOtx Transcription FactorsAnimalsCell Line, TumorCell MovementCell ProliferationCerebellar NeoplasmsFemaleHumansMaleMiceSignal TransductionMechanistic Target of Rapamycin Complex 2OTX2 protein, humanOtx Transcription Factorsgroup 3 medulloblastomaLMDmTORC2OTX2

Identifiers

PMID38674001
PMCPMC11050316
OpenAlexW4394891472

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.