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The Novel Roles of Connexin Channels and Tunneling Nanotubes in Cancer Pathogenesis

Public Health Research Institute (PHRI), Newark, NJ 07103, USA
Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers the State University of NJ, Newark, NJ 07103, USA
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA
GlaxoSmithKline, In-Silico Drug Discovery Unit, 1250 South Collegeville Road, Collegeville, PA 19426, USA
GlaxoSmithKline, In-Silico Drug Discovery Unit, Stevenage SG1 2NY, UK
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1270;
Received: 26 March 2018 / Revised: 13 April 2018 / Accepted: 18 April 2018 / Published: 24 April 2018
Neoplastic growth and cellular differentiation are critical hallmarks of tumor development. It is well established that cell-to-cell communication between tumor cells and “normal” surrounding cells regulates tumor differentiation and proliferation, aggressiveness, and resistance to treatment. Nevertheless, the mechanisms that result in tumor growth and spread as well as the adaptation of healthy surrounding cells to the tumor environment are poorly understood. A major component of these communication systems is composed of connexin (Cx)-containing channels including gap junctions (GJs), tunneling nanotubes (TNTs), and hemichannels (HCs). There are hundreds of reports about the role of Cx-containing channels in the pathogenesis of cancer, and most of them demonstrate a downregulation of these proteins. Nonetheless, new data demonstrate that a localized communication via Cx-containing GJs, HCs, and TNTs plays a key role in tumor growth, differentiation, and resistance to therapies. Moreover, the type and downstream effects of signals communicated between the different populations of tumor cells are still unknown. However, new approaches such as artificial intelligence (AI) and machine learning (ML) could provide new insights into these signals communicated between connected cells. We propose that the identification and characterization of these new communication systems and their associated signaling could provide new targets to prevent or reduce the devastating consequences of cancer. View Full-Text
Keywords: intercellular communication; gap junctions; hemichannels; tumor microtubes; glioblastoma intercellular communication; gap junctions; hemichannels; tumor microtubes; glioblastoma
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Valdebenito, S.; Lou, E.; Baldoni, J.; Okafo, G.; Eugenin, E. The Novel Roles of Connexin Channels and Tunneling Nanotubes in Cancer Pathogenesis. Int. J. Mol. Sci. 2018, 19, 1270.

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