Evidence map›Paper›PMID 27022132›Full record

ArticleNeuro-oncology2016

Cox-2-derived PGE2 induces Id1-dependent radiation resistance and self-renewal in experimental glioblastoma.

Peter J Cook, Rozario Thomas, Philip J Kingsley, Fumiko Shimizu, David C Montrose, Lawrence J Marnett, Viviane S Tabar, Andrew J Dannenberg, Robert Benezra

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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 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

54 citing papers in PubMed, 73 citations in OpenAlex.

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  13. The role of lipid metabolism in cancer radioresistance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
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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

9 authors at 3 institutions in 1 country.

Peter J CookCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Rozario ThomasCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Philip J KingsleyCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Fumiko ShimizuCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
David C MontroseCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Lawrence J MarnettCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Viviane S TabarCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Andrew J DannenbergCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.).
Robert BenezraCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York (P.J.C., R.T., R.B.); Department of Molecular Biology, Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York (R.T.); Departments of Biochemistry, Chemistry, and Pharmacology, A.B. Hancock Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, Vanderbilt University School of Medicine, Nashville, Tennessee (P.J.K., L.J.M.); Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York (F.S., V.S.T); Department of Medicine, Weill Cornell Medical College, New York, (D.C.M, A.J.D.) r-benezra@ski.mskcc.org ajdannen@med.cornell.edu.
Memorial Sloan Kettering Cancer Center · USCornell University · USVanderbilt University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundIn glioblastoma (GBM), Id1 serves as a functional marker for self-renewing cancer stem-like cells. We investigated the mechanism by which cyclooxygenase-2 (Cox-2)-derived prostaglandin E2 (PGE2) induces Id1 and increases GBM self-renewal and radiation resistance.

methodsMouse and human GBM cells were stimulated with dimethyl-PGE2 (dmPGE2), a stabilized form of PGE2, to test for Id1 induction. To elucidate the signal transduction pathway governing the increase in Id1, a combination of short interfering RNA knockdown and small molecule inhibitors and activators of PGE2 signaling were used. Western blotting, quantitative real-time (qRT)-PCR, and chromatin immunoprecipitation assays were employed. Sphere formation and radiation resistance were measured in cultured primary cells. Immunohistochemical analyses were carried out to evaluate the Cox-2-Id1 axis in experimental GBM.

resultsIn GBM cells, dmPGE2 stimulates the EP4 receptor leading to activation of ERK1/2 MAPK. This leads, in turn, to upregulation of the early growth response1 (Egr1) transcription factor and enhanced Id1 expression. Activation of this pathway increases self-renewal capacity and resistance to radiation-induced DNA damage, which are dependent on Id1.

conclusionsIn GBM, Cox-2-derived PGE2 induces Id1 via EP4-dependent activation of MAPK signaling and the Egr1 transcription factor. PGE2-mediated induction of Id1 is required for optimal tumor cell self-renewal and radiation resistance. Collectively, these findings identify Id1 as a key mediator of PGE2-dependent modulation of radiation response and lend insight into the mechanisms underlying radiation resistance in GBM patients.

Indexed as

AnimalsBlotting, WesternBrain NeoplasmsChromatin ImmunoprecipitationCyclooxygenase 2DinoprostoneEnzyme-Linked Immunosorbent AssayGene Knockdown TechniquesGlioblastomaHumansImmunohistochemistryInhibitor of Differentiation Protein 1MiceRadiation ToleranceReal-Time Polymerase Chain ReactionSignal TransductionCyclooxygenase 2DinoprostoneInhibitor of Differentiation Protein 1Cox-2glioblastomaId1PGE2radioresistance

Identifiers

PMID27022132
PMCPMC5035519
OpenAlexW2313572017

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.