ArticleCancer cell2017
MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma.
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Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 2 of them syntheses that pooled it.
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156citing papers in PubMed, 2 pooled it
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Who cites it
156 citing papers in PubMed, 2 syntheses or guidelines pooled it, 257 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Autophagy inhibition sensitizes radiotherapy responses in high-grade mutant IDH1 glioma.Nature communications · 2026Article
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- MST4 plays dual roles in lung adenocarcinoma by regulating homeostasis of wild-type and mutant p53 protein.Oncogene · 2026Article
- Phosphoproteomic profiling reveals post-translational dysregulation in Huntington's disease patient-derived neurons.Cellular & molecular biology letters · 2026Article
- DNA methylation-mediated memory of obesity in CD4 T lymphocytes perpetuates immune dysregulation.EMBO reports · 2026Article
- BRI3 Orchestrates Lipid Metabolism and Autophagy in Glioblastoma: Implications for Tumor Cell Resilience.Biochemical genetics · 2026Article
- Systematic analyses to explore kinase gene set-based signature in glioma, in which WEE1 contributes to tumor progression.Discover oncology · 2026Article
- The MST4-14-3-3ζ complex promotes pancreatic cancer by activating YAP.Biology direct · 2026Article
- NANP targeting radiosensitizes glioblastoma through TNFR1 sialylation-driven mesenchymal shift.Nature communications · 2026Article
- Phosphoproteome landscape of ARID1A and its implications in DNA damage response and breast cancer pathogenesis.Discover oncology · 2026Article
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- The BRAF V600E/MEK/ERK/METTL3 positive feedback loop regulates autophagy and promotes stemness and invasiveness in glioblastoma via mJournal of experimental & clinical cancer research : CR · 2025Article
- Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity.Nature communications · 2025Article
- Autophagy-Targeting Nanomedicine: Strike at the Heart of the Cancer via Precise Modulation of Autophagy.Exploration (Beijing, China) · 2025Review
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.Neuro-oncology · 2025Article
- Autophagy Upregulation in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma Uncovers a Novel Therapeutic Target.Research square · 2025Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 2 countries.
Tianzhi HuangKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Chung Kwon KimKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Angel A AlvarezKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Rajendra P PangeniKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Xuechao WanKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Xiao SongKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Taiping ShiKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Yongyong YangKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Namratha SastryKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Craig M HorbinskiThe Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Songjian LuDepartment of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15206, USA.
Roger StuppKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
John A KesslerKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ryo NishikawaDepartment of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama 350-1298, Japan.
Ichiro NakanoDepartment of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Erik P SulmanDepartment of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Houston, TX 77030, USA.
Xinghua LuDepartment of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA 15206, USA.
Charles David JamesThe Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Xiao-Ming YinDepartment of Pathology & Laboratory Medicine, Indiana University, Indianapolis, IN 46202, USA.
Bo HuKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: bo.hu@northwestern.edu.
Shi-Yuan ChengKen & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; The Lou and Jean Malnati Brain Tumor Institute, The Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address: shiyuan.cheng@northwestern.edu.
Northwestern University · USNeurological Surgery · USUniversity of Pittsburgh · USIndiana University – Purdue University Indianapolis · USSaitama Medical University · JPThe University of Texas MD Anderson Cancer Center · USUniversity of Alabama at Birmingham · US
Funding
The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI E. Antonio Chiocca · 2013 to 2026
$26.0MTRAINING PROGRAM IN SIGNAL TRANSDUCTION AND CANCERT32CA070085 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LEONIDAS C. PLATANIAS · 1997 to 2026
$5.7MInterpretable deep learning models for translational medicine RenewalR01LM012011 · NLM · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Tanner J. Freeman, XINGHUA LU · 2015 to 2026
$3.6MInduced Pluripotent Stem Cell Core for NiNDS InvestigatorsP30NS081774 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KESSLER, JOHN A · 2012 to 2016
$2.3MSignal integration of the death receptor pathwaysR01CA083817 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YIN, XIAO-MING · 2000 to 2010
$2.1MThe dynamics and mechanisms of autophagy in ethanol - induced liver pathogenesisR01AA021751 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI TSUKAMOTO, HIDEKAZU, YIN, XIAO-MING · 2013 to 2017
$2.1MGlioblastoma Phenotype Modulation Through miRNA Control of Wnt SignalingR01NS093843 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.8MBRAF Mutation in Malignant Astrocytoma Origin, Evolution, and Response to TherapyR01NS080619 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAMES, CHARLES DAVID, PETRITSCH, CLAUDIA KATHARINA · 2012 to 2016
$1.8MTissue Factor as a Key Determinant of IDH1 Mutant versus IDH1 Wild-type Glioma Thrombosis and MalignancyR01NS102669 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HORBINSKI, CRAIG MICHAEL · 2017 to 2021
$1.7MAutophagy Regulation of Glioblastoma Tumorigenesis and Responses to TherapyR01NS095634 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CHENG, SHI-YUAN · 2015 to 2019
$1.7MCdk4/6 Inhibitor Therapy for Glioblastoma MultiformeR01CA159467 · NCI · GEORGETOWN UNIVERSITY · PI JAMES, CHARLES DAVID, WALDMAN, TODD A · 2012 to 2016
$1.6MThe impact of growth modulation of liver carcinogenesisR01CA111456 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YIN, XIAO-MING · 2005 to 2009
$1.4MNCI NIH HHS P01 CA163205NCI NIH HHS R01 CA083817NCI NIH HHS R01 CA111456NCI NIH HHS R01 CA159467NCI NIH HHS R21 CA175875NCI NIH HHS T32 CA070085NIAAA NIH HHS R01 AA021751NIMHD NIH HHS L32 MD010147NINDS NIH HHS P30 NS081774NINDS NIH HHS R01 NS080619NINDS NIH HHS R01 NS083767NINDS NIH HHS R01 NS093843NINDS NIH HHS R01 NS095634NINDS NIH HHS R01 NS102669NLM NIH HHS K99 LM011673NLM NIH HHS R00 LM011673NLM NIH HHS R01 LM012011
Abstract
ATG4B stimulates autophagy by promoting autophagosome formation through reversible modification of ATG8. We identify ATG4B as a substrate of mammalian sterile20-like kinase (STK) 26/MST4. MST4 phosphorylates ATG4B at serine residue 383, which stimulates ATG4B activity and increases autophagic flux. Inhibition of MST4 or ATG4B activities using genetic approaches or an inhibitor of ATG4B suppresses autophagy and the tumorigenicity of glioblastoma (GBM) cells. Furthermore, radiation induces MST4 expression, ATG4B phosphorylation, and autophagy. Inhibiting ATG4B in combination with radiotherapy in treating mice with intracranial GBM xenograft markedly slows tumor growth and provides a significant survival benefit. Our work describes an MST4-ATG4B signaling axis that influences GBM autophagy and malignancy, and whose therapeutic targeting enhances the anti-tumor effects of radiotherapy.
Indexed as
AnimalsAutophagyAutophagy-Related ProteinsBrain NeoplasmsCarcinogenesisCell Line, TumorCysteine EndopeptidasesGlioblastomaHippo KinasesHumansMiceMice, NudePhosphorylationProtein Serine-Threonine KinasesRadiation ToleranceXenograft Model Antitumor AssaysATG4B protein, humanAutophagy-Related ProteinsCysteine EndopeptidasesHippo KinasesProtein Serine-Threonine KinasesSTK26 protein, humanATG4BATG4B inhibitor NSC185058autophagycombination therapyglioblastomaglioma stem-like cellsMST4/STK26phosphorylationtumorigenicitytumor response to radiation
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