ArticleNeuro-oncology2015
Connexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy.
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Article in Neuro-oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas.Medical gas research · 2027Review
- Calcium-modulated GJB6-GRHL3 positive feedback loop attenuates ESCC progression through AKT signaling pathway inhibition.NPJ precision oncology · 2026Article
- Connexin-Pannexin duality in glioblastoma.Cell and tissue research · 2026Review
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Non-Immune-Mediated, p27-Associated, Growth Inhibition of Glioblastoma by Class-II-Transactivator (CIITA).Cells · 2024Article
- Article
- Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma.Cancers · 2023Article
- The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintenance.Biology · 2023Review
- Tumor-related molecular determinants of neurocognitive deficits in patients with diffuse glioma.Neuro-oncology · 2022Article
- Glioblastoma-Astrocyte Connexin 43 Gap Junctions Promote Tumor Invasion.Molecular cancer research : MCR · 2022Article
- Connexin 43 confers chemoresistance through activating PI3K.Oncogenesis · 2022Article
- Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- A KRAS-Associated Signature for Prognostic, Immune and Chemical Anti-Cancer Drug-Response Prediction in Colon Cancer.Frontiers in pharmacology · 2022Article
- The 3.0 Cell Communication: New Insights in the Usefulness of Tunneling Nanotubes for Glioblastoma Treatment.Cancers · 2021Review
- Development of a 15-gene signature for predicting prognosis in advanced colorectal cancer.Bioengineered · 2020Article
- Connexins-Therapeutic Targets in Cancers.International journal of molecular sciences · 2020Review
- Endothelial-Tumor Cell Interaction in Brain and CNS Malignancies.International journal of molecular sciences · 2020Review
- Role of Connexins 30, 36, and 43 in Brain Tumors, Neurodegenerative Diseases, and Neuroprotection.Cells · 2020Review
- Effect of bovine leukemia virus (BLV) infection on bovine mammary epithelial cells RNA-seq transcriptome profile.PloS one · 2020Article
- Connexins in cancer: bridging the gap to the clinic.Oncogene · 2019Review
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Authors and funding
14 authors at 4 institutions in 4 countries.
Maria ArtesiDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Jerome KroonenDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Markus BredelDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Minh Nguyen-KhacDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Manuel DeprezDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Laurent SchoysmanDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Christophe PouletDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Arnab ChakravartiDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Hyunsoo KimDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Denise ScholtensDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Tatjana SeuteDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Bernard RogisterDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Vincent BoursDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
Pierre A RobeDepartment of Human Genetics, CBIG/GIGA Research Center, University of Liège, Liège, Belgium (M.A., J.K., M.N.-K., L.S., C.P., V.B., P.A.R.); Department of Neurology and Neurosurgery and T. and P. Bonhenn Neuro-Oncology Laboratory, University Hospital of Utrecht, Utrecht, Netherlands (J.K., L.S., T.S., P.A.R.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Chicago, Illinois (D.S.); Center for Population Health Sciences, Institute for Public Health and Medicine, Northwestern University, Chicago (D.S.); Division of Neuropathology, University Hospital of Liège, Liège, Belgium (M.D.); Division of Neurobiology, CBIG/GIGA Research Center, University Hospital of Liège, Liège, Belgium (B.R.); Department of Radiation Oncology, Arthur G James Comprehensive Cancer Center and Richard L. Solove Research Institute, The Ohio State University Medical Center, Columbus, Ohio (A.C., P.A.R.); Department of Radiation Oncology, Hazelrig-Salter Radiation Oncology Center and UAB Comprehensive Cancer Center, Birmingham, Alabama (M.B., H.K.).
University of Liège · BEUtrecht University · NLCentre Hospitalier Universitaire de Liège · BEUniversity of Alabama at Birmingham · US
Funding
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3MNCI NIH HHS P30 CA016058
Abstract
backgroundGlioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress.
methodsWe analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors.
resultsThe GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90-dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress.
conclusionThese results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors.
Indexed as
AnimalsBiomarkers, TumorBrain NeoplasmsCell Line, TumorCell ProliferationConnexin 30ConnexinsGene DeletionGliomaHeterograftsHSP90 Heat-Shock ProteinsHumansInhibitor of Apoptosis ProteinsKaplan-Meier EstimateMiceMitochondriaBiomarkers, TumorBIRC5 protein, humanConnexin 30ConnexinsGJB6 protein, humanHSP90 Heat-Shock ProteinsInhibitor of Apoptosis ProteinsRNA, MessengerSurvivinconnexin 30glioblastomamitochondriaproliferationradiation resistance
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