ArticleCell reports2022
SerpinB3 drives cancer stem cell survival in glioblastoma.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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Who cites it
25 citing papers in PubMed, 26 citations in OpenAlex.
- A Picomolar MBP-Binding Nanobody for Target Enrichment and Modular Complex Engineering.ACS bio & med chem Au · 2026Article
- 1-Piperidine Propionic Acid Inhibits PAR2/SerpinB3 Signaling and Reduces Glioblastoma Tumor Aggressiveness.International journal of molecular sciences · 2026Article
- Radiotherapy resistance in glioblastoma: Mechanistic insights and novel therapeutic approaches (Review).International journal of oncology · 2026Review
- SerpinB7 promotes c-Myc-mediated glycolysis by interacting with ANXA2 to facilitate the progression of non-small cell lung cancer.Molecular cancer · 2026Article
- The promising role of cathepsins as biomarkers and therapeutic targets in glioblastoma.Discover oncology · 2026Review
- Lipocalin 2 orchestrates resistance to ferroptosis via AXL.Cell reports · 2026Article
- SERPINB3 enhances NPM1 sumoylation via inhibiting SENP3's activity and promotes lung tumorigenesis.Cell death & disease · 2025Article
- Intracranial injection of genetically modified, mosquito non-transmissible Zika virus: Safety in primates and ramifications for brain tumor therapy.Cell reports. Medicine · 2025Article
- MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The impact of serpinB3-PD polymorphism on the prognosis of patients with hepatocellular carcinoma.Translational oncology · 2025Article
- Proteomic Profiling of Pre- and Post-Surgery Saliva of Glioblastoma Patients: A Pilot Investigation.International journal of molecular sciences · 2024Article
- Antipsychotics possess anti-glioblastoma activity by disrupting lysosomal function and inhibiting oncogenic signaling by stabilizing PTEN.Cell death & disease · 2024Article
- Article
- WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling.International journal of oral science · 2024Article
- SerpinB3/4 Expression Is Associated with Poor Prognosis in Patients with Cholangiocarcinoma.Cancers · 2024Article
- 'Slicing' glioblastoma drivers with the Swiss cheese model.Trends in cancer · 2024Review
- SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer.Cell reports · 2023Article
- Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.Cell reports. Medicine · 2023Article
- Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases.International journal of molecular sciences · 2023Article
- SERPINB5 is a prognostic biomarker and promotes proliferation, metastasis and epithelial-mesenchymal transition (EMT) in lung adenocarcinoma.Thoracic cancer · 2023Article
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Authors and funding
19 authors at 7 institutions in 1 country.
Adam LaukoDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA; Medical Scientist Training Program, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Josephine VolovetzDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA.
Soumya M TuragaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA.
Defne BayikDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Daniel J SilverDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Kelly MitchellDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Erin E Mulkearns-HubertDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA.
Dionysios C WatsonDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA; Division of Hematology/Oncology, University Hospitals Cleveland Medical Center, Cleveland, OH 44106, USA.
Kiran DesaiDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Manav MidhaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Jing HaoDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Kathleen McCortneyDepartment of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Alicia SteffensDepartment of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Ulhas NaikDepartment of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Manmeet S AhluwaliaMiami Cancer Institute, Baptist Health South Florida, Miami, FL 33176, USA.
Shideng BaoCleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA.
Craig HorbinskiDepartment of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurosurgery, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Jennifer S YuCleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA; Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44106, USA; Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH 44106, USA.
Justin D LathiaDepartment of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44106, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, OH 44115, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, OH 44106, USA. Electronic address: lathiaj@ccf.org.
Cleveland Clinic Lerner College of Medicine · USNorthwestern University · USCleveland State University · USBaptist Hospital of Miami · USCleveland Clinic · USThomas Jefferson University · USUniversity Hospitals of Cleveland · US
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007250 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI HUANG, ALEX YEE-CHEN · 1985 to 2023
$33.4MSex-specific differences in the tumor microenvironment alter glioblastoma growthP01CA245705 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI Daniel J Silver · 2020 to 2026
$15.0MTRAINING IN GEOGRAPHIC MEDICINE &INFECTIOUS DISEASET32AI007024 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI KAZURA, JAMES WALTER · 1985 to 2020
$4.5MContribution of Myeloid-Derived Suppressor Cells to Neuro-Inflammatory Alterations and Disease Progression in GlioblastomaR35NS127083 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI Justin D. Lathia · 2022 to 2026
$3.1MNRSA Training CoreTL1TR002549 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI HARDING, CLIFFORD V · 2018 to 2022
$2.9MTissue 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
$1.7MDeciphering MDSC function for GBM targetingR01NS109742 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D., VOGELBAUM, MICHAEL A. · 2019 to 2023
$1.7MInteraction between Tissue Factor, Junctional Adhesion Molecule-A, and Integrin B1 to drive self-renewal in glioblastomaR01NS117104 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI HORBINSKI, CRAIG MICHAEL, LATHIA, JUSTIN D. · 2020 to 2024
$1.5MRole of myeloid-derived suppressor cells in local and systemic immunosuppression in glioblastomaK99CA248611 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAYIK WATSON, DEFNE · 2021 to 2022
$241kRole of SerpinB3 in glioblastoma cancer stem cellsF30CA250254 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LAUKO, ADAM · 2021 to 2024
$191kNCATS NIH HHS TL1 TR002549NCI NIH HHS F30 CA250254NCI NIH HHS K99 CA248611NCI NIH HHS P01 CA245705NIAID NIH HHS T32 AI007024NIGMS NIH HHS T32 GM007250NINDS NIH HHS R01 NS102669NINDS NIH HHS R01 NS109742NINDS NIH HHS R01 NS117104NINDS NIH HHS R35 NS127083
Abstract
Despite therapeutic interventions for glioblastoma (GBM), cancer stem cells (CSCs) drive recurrence. The precise mechanisms underlying CSC resistance, namely inhibition of cell death, are unclear. We built on previous observations that the high cell surface expression of junctional adhesion molecule-A drives CSC maintenance and identified downstream signaling networks, including the cysteine protease inhibitor SerpinB3. Using genetic depletion approaches, we found that SerpinB3 is necessary for CSC maintenance, survival, and tumor growth, as well as CSC pathway activation. Knockdown of SerpinB3 also increased apoptosis and susceptibility to radiation therapy. SerpinB3 was essential to buffer cathepsin L-mediated cell death, which was enhanced with radiation. Finally, we found that SerpinB3 knockdown increased the efficacy of radiation in pre-clinical models. Taken together, our findings identify a GBM CSC-specific survival mechanism involving a cysteine protease inhibitor, SerpinB3, and provide a potential target to improve the efficacy of GBM therapies against therapeutically resistant CSCs.
Indexed as
GlioblastomaCysteine Proteinase InhibitorsHumansNeoplastic Stem CellsSignal TransductionCysteine Proteinase Inhibitorscancer stem cellcathepsin LCP: Cancerglioblastomalysosomal-mediated cell deathSerpinB3
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