Evidence map›Paper›PMID 26136493›Full record

ArticleNeuro-oncology2016

Insulin-mediated signaling promotes proliferation and survival of glioblastoma through Akt activation.

Yuanying Gong, Yufang Ma, Maksim Sinyuk, Sudan Loganathan, Reid C Thompson, Jann N Sarkaria, Wenbiao Chen, Justin D Lathia, Bret C Mobley, Stephen W Clark and 1 more

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

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.

  1. Pooled it
  2. A Phase 0 Trial of Ceritinib in Patients with Brain Metastases and Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
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  19. Tumor Drug Concentration and Phosphoproteomic Profiles After Two Weeks of Treatment With Sunitinib in Patients with Newly Diagnosed Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    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

11 authors at 4 institutions in 1 country.

Yuanying GongDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Yufang MaDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Maksim SinyukDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Sudan LoganathanDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Reid C ThompsonDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Jann N SarkariaDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Wenbiao ChenDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Justin D LathiaDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Bret C MobleyDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Stephen W ClarkDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Jialiang WangDepartment of Neurological Surgery (Y.G., Y.M., R.C.T., S.W.C., J.W.), Department of Molecular Physiology and Biophysics (W.C.), Department of Neurology (S.W.C.), Department of Pathology, Microbiology and Immunology (B.C.M.), and Department of Cancer Biology and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee (J.W.); Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio (M.S., J.D.L.); Department of Neuroscience and Pharmacology, Meharry Medical College, Nashville, Tennessee (S.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (J.N.S.).
Mayo Clinic · USNeurological Surgery · USVanderbilt University · USCleveland Clinic · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MATTHEW J TYSKA · 1995 to 2026
$172.8M
THE MEHARRY RISE INITIATIVER25GM059994 · NIGMS · MEHARRY MEDICAL COLLEGE · PI MOTLEY-JOHNSON, EVANGELINE D · 1999 to 2021
$23.0M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
TRAINING IN PHARMACOLOGICAL SCIENCEST32GM007628 · NIGMS · VANDERBILT UNIVERSITY · PI BARNETT, JOEY VICTOR, KAVALALI, EGE T · 1985 to 2022
$11.2M
Meharry RCMI Program in Women's Health ResearchG12MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI HILDRETH, JAMES E · 2012 to 2016
$7.8M
Targeting Radiation Resistance in Glioblastoma Stem CellsR01CA166492 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI FREEMAN, MICHAEL L. · 2013 to 2017
$1.6M
NCI NIH HHS 1R01CA166492NCI NIH HHS 5K12CA090625NCI NIH HHS K12 CA090625NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA166492NIGMS NIH HHS R25 GM059994NIGMS NIH HHS T32 GM007628NIMHD NIH HHS G12 MD007586
6 · The paper itself

Abstract

backgroundMetabolic complications such as obesity, hyperglycemia, and type 2 diabetes are associated with poor outcomes in patients with glioblastoma. To control peritumoral edema, use of chronic high-dose steroids in glioblastoma patients is common, which can result in de novo diabetic symptoms. These metabolic complications may affect tumors via profound mechanisms, including activation of insulin receptor (InsR) and the related insulin-like growth factor 1 receptor (IGF1R) in malignant cells.

methodsIn the present study, we assessed expression of InsR in glioblastoma surgical specimens and glioblastoma response to insulin at physiologically relevant concentrations. We further determined whether genetic or pharmacological targeting of InsR affected oncogenic functions of glioblastoma in vitro and in vivo.

resultsWe showed that InsR was commonly expressed in glioblastoma surgical specimens and xenograft tumor lines, with mitogenic isoform-A predominating. Insulin at physiologically relevant concentrations promoted glioblastoma cell growth and survival, potentially via Akt activation. Depletion of InsR impaired cellular functions and repressed orthotopic tumor growth. The absence of InsR compromised downstream Akt activity, but yet stimulated IGF1R expression. Targeting both InsR and IGF1R with dual kinase inhibitors resulted in effective blockade of downstream signaling, loss of cell viability, and repression of xenograft tumor growth.

conclusionsTaken together, our work suggests that glioblastoma is sensitive to the mitogenic functions of insulin, thus significant insulin exposure imposes risks to glioblastoma patients. Additionally, dual inhibition of InsR and IGF1R exhibits promise for treating glioblastoma.

Indexed as

AnimalsAntigens, CDBrain NeoplasmsCell ProliferationCell SurvivalFemaleGlioblastomaHumansInsulinInsulin-Like Growth Factor IInsulin-Like Growth Factor IIMice, NudeProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptor, InsulinReceptors, SomatomedinAntigens, CDIGF1 protein, humanIGF1R protein, humanIGF2 protein, humanINSR protein, humanInsulinInsulin-Like Growth Factor IInsulin-Like Growth Factor IIProto-Oncogene Proteins c-aktReceptor, IGF Type 1Receptor, InsulinReceptors, SomatomedinAktglioblastomaIGF1Rinsulininsulin receptor

Identifiers

PMID26136493
PMCPMC4677408
OpenAlexW2211132464

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Registered trials

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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.