Differential Connexin Function Enhances Self-Renewal in Glioblastoma
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), bu...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715004088 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Masahiro Hitomi Loic P. Deleyrolle Erin E. Mulkearns-Hubert Awad Jarrar Meizhang Li Maksim Sinyuk Balint Otvos Sylvain Brunet William A. Flavahan Christopher G. Hubert Winston Goan James S. Hale Alvaro G. Alvarado Ao Zhang Mark Rohaus Muna Oli Vinata Vedam-Mai Jeff M. Fortin Hunter S. Futch Benjamin Griffith Qiulian Wu Chun-hong Xia Xiaohua Gong Manmeet S. Ahluwalia Jeremy N. Rich Brent A. Reynolds Justin D. Lathia |
| spellingShingle |
Masahiro Hitomi Loic P. Deleyrolle Erin E. Mulkearns-Hubert Awad Jarrar Meizhang Li Maksim Sinyuk Balint Otvos Sylvain Brunet William A. Flavahan Christopher G. Hubert Winston Goan James S. Hale Alvaro G. Alvarado Ao Zhang Mark Rohaus Muna Oli Vinata Vedam-Mai Jeff M. Fortin Hunter S. Futch Benjamin Griffith Qiulian Wu Chun-hong Xia Xiaohua Gong Manmeet S. Ahluwalia Jeremy N. Rich Brent A. Reynolds Justin D. Lathia Differential Connexin Function Enhances Self-Renewal in Glioblastoma Cell Reports |
| author_facet |
Masahiro Hitomi Loic P. Deleyrolle Erin E. Mulkearns-Hubert Awad Jarrar Meizhang Li Maksim Sinyuk Balint Otvos Sylvain Brunet William A. Flavahan Christopher G. Hubert Winston Goan James S. Hale Alvaro G. Alvarado Ao Zhang Mark Rohaus Muna Oli Vinata Vedam-Mai Jeff M. Fortin Hunter S. Futch Benjamin Griffith Qiulian Wu Chun-hong Xia Xiaohua Gong Manmeet S. Ahluwalia Jeremy N. Rich Brent A. Reynolds Justin D. Lathia |
| author_sort |
Masahiro Hitomi |
| title |
Differential Connexin Function Enhances Self-Renewal in Glioblastoma |
| title_short |
Differential Connexin Function Enhances Self-Renewal in Glioblastoma |
| title_full |
Differential Connexin Function Enhances Self-Renewal in Glioblastoma |
| title_fullStr |
Differential Connexin Function Enhances Self-Renewal in Glioblastoma |
| title_full_unstemmed |
Differential Connexin Function Enhances Self-Renewal in Glioblastoma |
| title_sort |
differential connexin function enhances self-renewal in glioblastoma |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2015-05-01 |
| description |
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. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124715004088 |
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1725081694243913728 |
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doaj-494a4a229a984f468e7f3e93cceb546e2020-11-25T01:32:30ZengElsevierCell Reports2211-12472015-05-011171031104210.1016/j.celrep.2015.04.021Differential Connexin Function Enhances Self-Renewal in GlioblastomaMasahiro Hitomi0Loic P. Deleyrolle1Erin E. Mulkearns-Hubert2Awad Jarrar3Meizhang Li4Maksim Sinyuk5Balint Otvos6Sylvain Brunet7William A. Flavahan8Christopher G. Hubert9Winston Goan10James S. Hale11Alvaro G. Alvarado12Ao Zhang13Mark Rohaus14Muna Oli15Vinata Vedam-Mai16Jeff M. Fortin17Hunter S. Futch18Benjamin Griffith19Qiulian Wu20Chun-hong Xia21Xiaohua Gong22Manmeet S. Ahluwalia23Jeremy N. Rich24Brent A. Reynolds25Justin D. Lathia26Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USABerkeley Stem Cell Center, University of California, Berkeley, Berkeley, CA 94720, USABerkeley Stem Cell Center, University of California, Berkeley, Berkeley, CA 94720, USARose Ella Burkhardt Brain Tumor and Neuro Oncology Center, Cleveland Clinic, Cleveland, OH 44195, USAMolecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USADepartment of Neurosurgery, University of Florida, Gainesville, FL 32610-0261, USADepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44915, USAThe 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.http://www.sciencedirect.com/science/article/pii/S2211124715004088 |