ArticleCell reports2023
The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
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23 citing papers in PubMed, 24 citations in OpenAlex.
- CD97/Cells · 2026Review
- Uncovering the signaling networks of disseminated glioblastoma cells in vivo with INSIGHT.Nature communications · 2026Article
- Integrative Single-Cell and Spatial Transcriptomic Analyses Link Arachidonic Acid Metabolic Reprogramming to Proneural-to-Mesenchymal State Transition in Glioblastoma.Biomedicines · 2026Article
- T cell-engaging bispecific antibodies for myeloid malignancies: Targets, formats, and clinical challenges.Cell reports. Medicine · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Therapeutic targeting of adhesion GPCRs: a status update and future potential.Expert opinion on drug discovery · 2026Review
- Cytoplasmic tail diversity determines the effector bias of the adhesion GPCR ADGRL2.Cell chemical biology · 2026Article
- STING activation induces cytotoxic and immune responses in meningiomas via inflammatory cell death pathways.Nature communications · 2026Article
- Single-cell sequencing and network pharmacology coupled with molecular docking and experimental validation reveal the effects of YPFS on macrophages in stage I non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma.Cell discovery · 2025Article
- Cell populations in human breast cancers are molecularly and biologically distinct with age.Nature aging · 2025Article
- Engineering antibody-drug conjugates targeting an adhesion GPCR, CD97.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding ADGRE5: How Proteolytic Cleavage and Mechanical Forces Unleash Cellular Signals.Cells · 2025Article
- Article
- Cytoplasmic tail composition modulates the G protein and arrestin-3 signaling bias of the adhesion GPCR LPHN2.bioRxiv : the preprint server for biology · 2025Article
- CD97-directed CAR-T cells with enhanced persistence eradicate acute myeloid leukemia in diverse xenograft models.Cell reports. Medicine · 2025Article
- GPR56/ADGRG1 induces biased Rho-ROCK-MLC and JAK-STAT3 signaling to promote amoeboid-like morphology and IL-6 upregulation in melanoma cells.Cell communication and signaling : CCS · 2025Article
- Cell-type-specific regulators landscape and regulatory mechanisms underlying pyroptosis in uterine corpus endometrial carcinoma.Journal of Cancer · 2025Article
- CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells.Cell reports. Medicine · 2024Article
- Unveiling the Inflammatory Landscape of Recurrent Glioblastoma through Histological-Based Assessments.Cancers · 2024Review
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Authors and funding
33 authors at 6 institutions in 2 countries.
Niklas Ravn-BoessDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Nainita RoyDepartment of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Takamitsu HattoriLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Devin BreadyDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Hayley DonaldsonDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Christopher LawsonDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Cathryn LapierreDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Aryeh KormanMetabolomics Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Tori RodrickMetabolomics Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Enze LiuDepartment of Medicine, Division of Hematology/Oncology, Indiana University, Indianapolis, IN 46202, USA.
Joshua D FrensterDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Gabriele StephanDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Jordan WilcoxDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Alexis D CorradoLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Julia CaiDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Rebecca RonnenDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Shuai WangDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Sara HaddockDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Jonathan Sabio OrtizDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA.
Orin MishkitPreclinical Imaging Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Alireza Khodadadi-JamayranApplied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY 10016, USA.
Aris TsirigosApplied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY 10016, USA.
David FenyöDepartment of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA; Institute for Systems Genetics, NYU Grossman School of Medicine, New York, NY 10016, USA.
David ZagzagDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Julia DrubeInstitute for Molecular Cell Biology, Universitätsklinikum Jena, 07745 Jena, Germany.
Carsten HoffmannInstitute for Molecular Cell Biology, Universitätsklinikum Jena, 07745 Jena, Germany.
Fabiana PernaMoffitt Cancer Center, Tampa, FL 33612, USA.
Drew R JonesMetabolomics Laboratory, NYU Grossman School of Medicine, New York, NY 10016, USA.
Richard PossematoDepartment of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA.
Akiko KoideLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA.
Shohei KoideLaura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016, USA.
Christopher Y ParkDepartment of Pathology, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA.
Dimitris G PlacantonakisDepartment of Neurosurgery, NYU Grossman School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Kimmel Center for Stem Cell Biology, NYU Grossman School of Medicine, New York, NY 10016, USA; Brain and Spine Tumor Center, NYU Grossman School of Medicine, New York, NY 10016, USA; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA. Electronic address: dimitris.placantonakis@nyulangone.org.
New York University · USNYU Langone’s Laura and Isaac Perlmutter Cancer CenterJena University Hospital · DEIndiana University – Purdue University Indianapolis · USInstitute for Systems Biology · USMoffitt Cancer Center · US
Funding
Project-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5MVaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1MTraining Program in Cell BiologyT32GM136542 · NIGMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SMITH, SUSAN · 2020 to 2024
$3.0MAdhesion GPCR regulation of acute myeloid leukemia stem cells - Resubmission - 1R01CA251669 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PARK, CHRISTOPHER Y · 2021 to 2025
$3.0MDevelopmentally Regulated Enhancers and Chromatin Architecture in Human NeurogenesisR01NS124920 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Dimitris G. Placantonakis · 2022 to 2026
$2.7MThe role of GPR133 in glioblastomaR01NS102665 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PLACANTONAKIS, DIMITRIS G. · 2018 to 2022
$2.3MFingerprinting-Based Neuronal Fiber Identification in Brain SurgeryR01EB028774 · NIBIB · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BAETE, STEVEN H. · 2020 to 2023
$1.9MRational generation of high-performance recombinant antibodies to post-translational modificationsR21CA246457 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HATTORI, TAKAMITSU · 2020 to 2020
$620kCalcium dynamics and signaling in gliomaR21NS126806 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI PLACANTONAKIS, DIMITRIS G. · 2022 to 2022
$466kIdentification and molecular characterization of FGFR4 p.G388R variant signaling in cerebellar hemangioblastomasR21CA263402 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ZAGZAG, DAVID · 2021 to 2022
$431kNCATS NIH HHS UL1 TR001445NCI NIH HHS P30 CA016087NCI NIH HHS R01 CA251669NCI NIH HHS R21 CA246457NCI NIH HHS R21 CA263402NIBIB NIH HHS R01 EB028774NIGMS NIH HHS T32 GM136542NINDS NIH HHS R01 NS102665NINDS NIH HHS R01 NS124920NINDS NIH HHS R21 NS126806
Abstract
Glioblastoma (GBM) is the most common and aggressive primary brain malignancy. Adhesion G protein-coupled receptors (aGPCRs) have attracted interest for their potential as treatment targets. Here, we show that CD97 (ADGRE5) is the most promising aGPCR target in GBM, by virtue of its de novo expression compared to healthy brain tissue. CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures (PDGCs) in vitro and in vivo. We find that CD97 promotes glycolytic metabolism via the mitogen-activated protein kinase (MAPK) pathway, which depends on phosphorylation of its C terminus and recruitment of β-arrestin. We also demonstrate that THY1/CD90 is a likely CD97 ligand in GBM. Lastly, we show that an anti-CD97 antibody-drug conjugate selectively kills tumor cells in vitro. Our studies identify CD97 as a regulator of tumor metabolism, elucidate mechanisms of receptor activation and signaling, and provide strong scientific rationale for developing biologics to target it therapeutically in GBM.
Indexed as
GlioblastomaAntigens, CDHumansPhosphorylationReceptors, G-Protein-CoupledSignal TransductionADGRE5 protein, humanAntigens, CDReceptors, G-Protein-CoupledADGRE5adhesion G protein-coupled receptorantibody-drug conjugateCD97CP: Cancerglioblastomareceptor signalingWarburg metabolism
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