Differential Connexin Function Enhances Self-Renewal in Glioblastoma

Bibliographic Details
Title: Differential Connexin Function Enhances Self-Renewal in Glioblastoma
Authors: 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
Source: Cell Reports, Vol 11, Iss 7, Pp 1031-1042 (2015)
Publisher Information: Elsevier, 2015.
Publication Year: 2015
Collection: LCC:Biology (General)
Subject Terms: Biology (General), QH301-705.5
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2211-1247
Relation: http://www.sciencedirect.com/science/article/pii/S2211124715004088; https://doaj.org/toc/2211-1247
DOI: 10.1016/j.celrep.2015.04.021
Access URL: https://doaj.org/article/494a4a229a984f468e7f3e93cceb546e
Accession Number: edsdoj.494a4a229a984f468e7f3e93cceb546e
Database: Directory of Open Access Journals
More Details
ISSN:22111247
DOI:10.1016/j.celrep.2015.04.021
Published in:Cell Reports
Language:English