ArticleCancer cell2019
Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair.
Erratum issuedOpen access · bronzeAbstract read
In one paragraph
Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 81 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 1 pooled it
9.4field-weighted citation impact, top 1% of its field
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Fused inverse-normal method for integrated differential expression analysis of RNA-seq data.BMC bioinformatics · 2022Pooled it
- Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Impaired nuclear PTEN function drives macrocephaly, lymphadenopathy and late-onset cancer in PTEN hamartoma tumour syndrome.Disease models & mechanisms · 2026Article
- HAT1 as a Lactyltransferase to Promote DNA Repair Through RPA1 Lactylation in Glioblastoma.International journal of biological sciences · 2026Article
- The lncrnas: innovative multifunctional players of drug resistance in colorectal cancer.Cancer cell international · 2025Review
- The glycolytic enzyme PGK1 phosphorylates MORC2 to Confer radioresistance in pancreatic ductal adenocarcinoma.Cell death & disease · 2025Article
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- EZH2 inhibition and 5-azacytidine enhance antitumor immunity in PTEN-deficient glioblastoma by activation viral mimicry response.Journal for immunotherapy of cancer · 2025Article
- Post-translational modifications in DNA damage repair: mechanisms underlying temozolomide resistance in glioblastoma.Oncogene · 2025Review
- SIRT7 facilitates endometrial cancer progression by regulating PTEN stability in an estrogen-dependent manner.Nature communications · 2025Article
- Evolution of Molecular Biomarkers and Precision Molecular Therapeutic Strategies in Glioblastoma.Cancers · 2024Review
- CuO nanoparticles for glioma treatment in vitro and in vivo.Scientific reports · 2024Article
- DNA damage response in brain tumors: A Society for Neuro-Oncology consensus review on mechanisms and translational efforts in neuro-oncology.Neuro-oncology · 2024Review
- Article
- The Role of Long Noncoding RNAs (lncRNAs) in Esophageal Cancer Therapy Resistance and Metastasis.Biomedicines · 2024Review
- Drug resistance mechanisms in cancers: Execution of pro-survival strategies.Journal of biomedical research · 2024Article
- Correlation of PTEN signaling pathway and miRNA in breast cancer.Molecular biology reports · 2024Article
- Therapeutic Potential of Alpha-pinene in Breast Cancer: Targeting miR-21 and PTEN Gene Expression.Galen medical journal · 2024Article
- VEGFA/NRP-1/GAPVD1 axis promotes progression and cancer stemness of triple-negative breast cancer by enhancing tumor cell-macrophage crosstalk.International journal of biological sciences · 2024Article
- Single-cell transcriptomic analysis identifies downregulated phosphodiesterase 8B as a novel oncogene in IDH-mutant glioma.Frontiers in immunology · 2024Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
24 authors at 7 institutions in 4 countries.
Jianhui MaLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Jorge A BenitezLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Jie LiDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Shunichiro MikiLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Claudio Ponte de AlbuquerqueLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Thais GalatroDepartment of Neurology, Laboratory of Molecular and Cellular Biology, LIM15, School of Medicine, University of São Paulo, São Paulo, Brazil.
Laura OrellanaScience for Life Laboratory, 17121 Stockholm, Sweden; Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden; Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 114 18 Stockholm, Sweden.
Ciro ZancaLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Rachel ReedLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Antonia BoyerLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Tomoyuki KogaLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Nissi M VarkiDepartment of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Tim R FentonSchool of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Suely Kazue Nagahashi MarieDepartment of Neurology, Laboratory of Molecular and Cellular Biology, LIM15, School of Medicine, University of São Paulo, São Paulo, Brazil; Center for Studies of Cellular and Molecular Therapy (NAP-NETCEM-NUCEL), University of São Paulo, São Paulo, Brazil.
Erik LindahlScience for Life Laboratory, 17121 Stockholm, Sweden; Theoretical and Computational Biophysics, Department of Theoretical Physics, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden; Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, 114 18 Stockholm, Sweden.
Timothy C GahmanLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Andrew K ShiauLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
Huilin ZhouLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA.
John DeGrootDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Erik P SulmanDepartments of Radiation Oncology, Translational Molecular Pathology, and Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Webster K CaveneeLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Richard D KolodnerLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Cellular and Molecular Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Clark C ChenDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
Frank B FurnariLudwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0660, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: ffurnari@ucsd.edu.
Ludwig Cancer Research · USUniversity of Minnesota · USNordic Institute for Theoretical Physics · SEThe University of Texas MD Anderson Cancer Center · USUniversidade de São Paulo · BRUniversity of California San Diego · USUniversity of Kent · GB
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MVIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9MTropism Enhanced Oncolytic Adenovirus for the Treatment of Brain TumorsP50CA127001 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Juan Fueyo · 2008 to 2026
$41.2MSiglec Modulation of Inflammatory ResponsesP01HL107150 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LE, DZUNG T · 2011 to 2017
$18.0MENZYMATIC MECHANISMS OF GENETIC RECOMBINATIONR01GM026017 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Richard D Kolodner · 1985 to 2026
$10.5MGenotypic Interactions in Brain Cancer HeterogeneityR01NS080939 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FURNARI, FRANK · 2012 to 2022
$3.5MSuppression of duplication-mediated genome rearrangements by protein sumoylationR01GM116897 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ZHOU, HUILIN · 2015 to 2023
$2.6MTargeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7MOrbitrap Fusion Mass SpectrometerS10OD023498 · OD · LUDWIG INSTITUTE FOR CANCER RES LTD · PI ZHOU, HUILIN · 2017 to 2017
$600kNCI NIH HHS P30 CA016672NCI NIH HHS P30 CA023100NCI NIH HHS P50 CA127001NHLBI NIH HHS P01 HL107150NIGMS NIH HHS R01 GM026017NIGMS NIH HHS R01 GM116897NIH HHS S10 OD023498NINDS NIH HHS R01 NS080939NINDS NIH HHS R01 NS097649
Abstract
Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
Indexed as
AnimalsBrain NeoplasmsCell NucleusDNA RepairFemaleGliomaHumansMaleMicePhosphorylationPTEN PhosphohydrolasePyrimidinesRad51 RecombinaseRadiation ToleranceReceptor, Fibroblast Growth Factor, Type 2TyrosineFGFR2 protein, humanPD 173074PTEN PhosphohydrolasePTEN protein, humanPyrimidinesRAD51 protein, humanRad51 RecombinaseReceptor, Fibroblast Growth Factor, Type 2TyrosineDNA damageFGFR2GBMionizing radiation (IR)PTENtyrosine phosphorylation
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