ArticleCell reports2015
Differential connexin function enhances self-renewal in glioblastoma.
Open access · goldAbstract read
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Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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78citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% of its field
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Connexin 43 C-terminus directly inhibits the hyperphosphorylation of Akt/ERK through protein-protein interactions in glioblastoma.Cancer science · 2018Pooled it
- Detection of circulating tumour cell clusters in human glioblastoma.British journal of cancer · 2018Trial
- High levels of nitric oxide and peroxynitrite with protein nitration: a new therapeutic target for gliomas.Medical gas research · 2027Review
- Hypoxia Increases Connexin46 and Connexin43 Levels in KNS-42 Glioblastoma Cells.International journal of molecular sciences · 2026Article
- Mitochondrial connexin 43 modulates metabolic stress adaptation in glioma cell lines.Cell communication and signaling : CCS · 2025Article
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.Cell reports · 2025Article
- Connexin hemichannel blockade by abEC1.1 disrupts glioblastoma progression, suppresses invasiveness, and reduces hyperexcitability in preclinical models.Cell communication and signaling : CCS · 2025Article
- Connexin43 functions as a non-canonical phenotypic stability factor in promoting hybrid Epithelial/Mesenchymal phenotype in glioblastoma cells.Translational oncology · 2025Article
- Connexin 43 Role in Mitochondrial Transfer and Homeostasis in the Central Nervous System.Journal of cellular physiology · 2025Review
- Cytoplasmic connexin43-microtubule interactions promote glioblastoma stem-like cell maintenance and tumorigenicity.Cell death & disease · 2025Article
- Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator.Cell communication and signaling : CCS · 2025Article
- Chemoresistance and the tumor microenvironment: the critical role of cell-cell communication.Cell communication and signaling : CCS · 2024Review
- Pan-cancer ion transport signature reveals functional regulators of glioblastoma aggression.The EMBO journal · 2024Article
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
- Cell Cycle-Related FAM64A Could be Activated by TGF-β Signaling to Promote Glioma Progression.Cellular and molecular neurobiology · 2023Article
- Cellular Conversations in Glioblastoma Progression, Diagnosis and Treatment.Cellular and molecular neurobiology · 2023Review
- KI04 an Aminoglycosides-Derived Molecule Acts as an Inhibitor of Human Connexin46 Hemichannels Expressed in HeLa Cells.Biomolecules · 2023Article
- Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.International journal of molecular sciences · 2023Article
- Antiproliferative effect of boldine on neural progenitor cells and on glioblastoma cells.Frontiers in neuroscience · 2023Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 6 institutions in 1 country.
Masahiro HitomiDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA; Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.
Loic P DeleyrolleDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Erin E Mulkearns-HubertDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Awad JarrarDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Meizhang LiDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Maksim SinyukDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Balint OtvosDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Sylvain BrunetDepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
William A FlavahanDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Christopher G HubertDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Winston GoanDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
James S HaleDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Alvaro G AlvaradoDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA; Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.
Ao ZhangDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Mark RohausDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Muna OliDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Vinata Vedam-MaiDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Jeff M FortinDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Hunter S FutchDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Benjamin GriffithDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA.
Qiulian WuDepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA.
Chun-Hong XiaBerkeley Stem Cell Center, University of California, Berkeley, Berkeley, CA 94720, USA.
Xiaohua GongBerkeley Stem Cell Center, University of California, Berkeley, Berkeley, CA 94720, USA.
Manmeet S AhluwaliaRose Ella Burkhardt Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Jeremy N RichMolecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA; Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
Brent A ReynoldsDepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USA. Electronic address: brent.reynolds@neurosurgery.ufl.edu.
Justin D LathiaDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USA; Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA; Rose Ella Burkhardt Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USA; Case Comprehensive Cancer Center, Cleveland, OH 44106, USA. Electronic address: lathiaj@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of Florida · USCase Western Reserve University · USCleveland Clinic · USUniversity of California, Berkeley · USCase Comprehensive Cancer Center
Funding
Cataracts, Connexin Mutants and Genetic ModifiersR01EY013849 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI Xiaohua Gong · 2002 to 2026
$8.2MTargeting Ferritin in GlioblastomaR01CA169117 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI BAO, SHIDENG, CONNOR, JAMES ROBERT · 2013 to 2017
$2.7MMetabolism Informs Intertumoral & Intratumoral HeterogeneityR01NS087913 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NAKANO, ICHIRO, RICH, JEREMY N · 2014 to 2018
$2.0MTargeting Brain Tumor Stem Cells Through Novel Therapeutic CombinationsR01CA154130 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI RICH, JEREMY N · 2010 to 2014
$1.9MNovel adhesion mechanisms in glioblastoma stem cellsR01NS083629 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2013 to 2017
$1.7MConnexins and glioblastoma progressionR01NS089641 · NINDS · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2015 to 2019
$1.7MEnergy Stress in Brain Tumor Initiating Stem CellsR01NS089272 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RICH, JEREMY N · 2014 to 2018
$1.7MMicroenvironmental regulation of the cancer stem cell phenotype by integrin a6R00CA157948 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2012 to 2014
$725kCell-cell communication in CSC self renewal and breast cancer progressionR21CA191263 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D., REIZES, OFER · 2015 to 2016
$379kSlow cycling brain tumor cancer stem cellsR21CA141020 · NCI · UNIVERSITY OF FLORIDA · PI REYNOLDS, BRENT · 2009 to 2010
$322kMicroenvironmental modulation as a result of glioma therapyK99CA157948 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI LATHIA, JUSTIN D. · 2011 to 2011
$99kNCI NIH HHS CA112958NCI NIH HHS CA141020NCI NIH HHS CA154130NCI NIH HHS CA157948NCI NIH HHS CA169117NCI NIH HHS CA191263NCI NIH HHS K99 CA157948NCI NIH HHS R00 CA157948NCI NIH HHS R01 CA154130NCI NIH HHS R01 CA169117NCI NIH HHS R21 CA141020NCI NIH HHS R21 CA191263NEI NIH HHS R01 EY013849NINDS NIH HHS NS083629NINDS NIH HHS NS087913NINDS NIH HHS NS089272NINDS NIH HHS R01 NS083629NINDS NIH HHS R01 NS087913NINDS NIH HHS R01 NS089272NINDS NIH HHS R01 NS089641
Abstract
The coordination of complex tumor processes requires cells to rapidly modify their phenotype and is achieved by direct cell-cell communication through gap junction channels composed of connexins. Previous reports have suggested that gap junctions are tumor suppressive based on connexin 43 (Cx43), but this does not take into account differences in connexin-mediated ion selectivity and intercellular communication rate that drive gap junction diversity. We find that glioblastoma cancer stem cells (CSCs) possess functional gap junctions that can be targeted using clinically relevant compounds to reduce self-renewal and tumor growth. Our analysis reveals that CSCs express Cx46, while Cx43 is predominantly expressed in non-CSCs. During differentiation, Cx46 is reduced, while Cx43 is increased, and targeting Cx46 compromises CSC maintenance. The difference between Cx46 and Cx43 is reflected in elevated cell-cell communication and reduced resting membrane potential in CSCs. Our data demonstrate a pro-tumorigenic role for gap junctions that is dependent on connexin expression.
Indexed as
AnimalsBrain NeoplasmsCell CommunicationConnexin 43ConnexinsFluorescent Antibody TechniqueGap JunctionsGlioblastomaHeterograftsHumansImmunoblottingMembrane PotentialsNeoplastic Stem CellsPatch-Clamp TechniquesPolymerase Chain ReactionConnexin 43ConnexinsGJA1 protein, humanGJA3 protein, human
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