Evidence map›Paper›PMID 29996106›Full record

ArticleCell reports2018

Opposing Tumor-Promoting and -Suppressive Functions of Rictor/mTORC2 Signaling in Adult Glioma and Pediatric SHH Medulloblastoma.

Seçkin Akgül, Yinghua Li, Siyuan Zheng, Marcel Kool, Daniel M Treisman, Chaoyang Li, Yuan Wang, Susanne Gröbner, Tsuneo Ikenoue, Yiping Shen and 9 more

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

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

17 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Review
  3. RICTOR/mTORC2 downregulation in BRAFMolecular cancer · 2024
    Article
  4. mTOR hyperactivity andPathology oncology research : POR · 2024
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Sox2Neuro-oncology advances
    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

19 authors at 11 institutions in 3 countries.

Seçkin AkgülCellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Gilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA; Sid Faithfull Brain Cancer Research Laboratory, Cell & Molecular Biology Department, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
Yinghua LiGilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
Siyuan ZhengGreehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Marcel KoolHopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
Daniel M TreismanCellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Gilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
Chaoyang LiGilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
Yuan WangGilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA.
Susanne GröbnerHopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
Tsuneo IkenoueDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Yiping ShenCenter for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Sandra Camelo-PiraguaDepartment of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Gerald TomasekDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Sebastian StarkHopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
Vinay GuduguntlaDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
James F GusellaCenter for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Kun-Liang GuanDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Stefan M PfisterHopp Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Department of Hematology and Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Roel G W VerhaakJackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Yuan ZhuCellular and Molecular Biology Graduate Program, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Gilbert Family Neurofibromatosis Institute, Children's National Medical Center, Washington, DC 20010, USA; Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC 20010, USA; Center for Neuroscience Research, Children's National Medical Center, Washington, DC 20010, USA. Electronic address: yzhu@childrensnational.org.
University of Michigan · USChildren's National · USUniversity of California San Diego · USDeutschen Konsortium für Translationale Krebsforschung · DEGerman Cancer Research Center · DEHarvard University · USHopp Children's Cancer Center Heidelberg · DEJackson Laboratory · USMassachusetts General Hospital · USThe University of Texas Health Science Center at San Antonio · USUniversity Hospital Heidelberg · DE

Funding

QUANTITATION OF HUMAN BRAIN TUMOR THERAPY RESPONSE BY MRP01CA085878 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROSS, BRIAN D. · 2001 to 2017
$31.9M
The mTOR and Hippo pathway in cell growth and cancerR35CA196878 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GUAN, KUN-LIANG · 2015 to 2019
$4.0M
The role of mTORC1 in the development and therapeutic targeting of NF1-associatedR01NS073762 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, YUAN · 2011 to 2015
$1.8M
Cellular and molecular basis of malignant astrocytomaR01NS053900 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZHU, YUAN · 2006 to 2010
$1.6M
NCI NIH HHS P01 CA085878NCI NIH HHS R35 CA196878NINDS NIH HHS R01 NS053900NINDS NIH HHS R01 NS073762
6 · The paper itself

Abstract

Most human cancers arise from stem and progenitor cells by the sequential accumulation of genetic and epigenetic alterations, while cancer modeling typically requires simultaneous multiple oncogenic events. Here, we show that a single p53 mutation, despite causing no defect in the mouse brain, promoted neural stem and progenitor cells to spontaneously accumulate oncogenic alterations, including loss of multiple chromosomal (chr) regions syntenic to human chr10 containing Pten, forming malignant gliomas with PI3K/Akt activation. Rictor/mTORC2 loss inhibited Akt signaling, greatly delaying and reducing glioma formation by suppressing glioma precursors within the subventricular zone stem cell niche. Rictor/mTORC2 loss delayed timely differentiation of granule cell precursors (GCPs) during cerebellar development, promoting sustained GCP proliferation and medulloblastoma formation, which recapitulated critical features of TP53 mutant sonic hedgehog (SHH) medulloblastomas with GLI2 and/or N-MYC amplification. Our study demonstrates that Rictor/mTORC2 has opposing functions in neural stem cells and GCPs in the adult and the developing brain, promoting malignant gliomas and suppressing SHH-medulloblastoma formation, respectively.

Indexed as

Signal TransductionAdultAnimalsBasic Helix-Loop-Helix ProteinsCarcinogenesisCell DifferentiationCell ProliferationChildGenome, HumanGliomaHedgehog ProteinsHumansMechanistic Target of Rapamycin Complex 2MedulloblastomaMiceMutationATOH1 protein, humanBasic Helix-Loop-Helix ProteinsHedgehog ProteinsMechanistic Target of Rapamycin Complex 2Proto-Oncogene Proteins c-aktRapamycin-Insensitive Companion of mTOR ProteinRICTOR protein, humanSHH protein, humanTumor Suppressor Protein p53Aktglioblastomamammalian target of rapamycin complex 2medulloblastomamTORC2p53phosphatidylinositol 3-kinase pathwayPI3KPtenRictor

Identifiers

PMID29996106
PMCPMC6116735
OpenAlexW2875192670

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.