Gap junctions and connexins as therapeutic targets in cancer.
BACKGROUND
Connexins (Cxs) and gap junctional intercellular communications (GJICs) play roles in cancer development, growth and metastasis. Experimental studies suggest that targeting Cxs may be a novel technique, either to inhibit tumor cell growth directly or to sensitize to various therapies.


METHODS
A brief introduction to the role of Cxs in cancer. The focus is mainly on data available in the literature regarding therapeutic aspects.


RESULTS
This article reviews the various strategies that take advantage of gap junctions and connexins to eliminate cancer cells, including use of the bystander effect (BE) in gene therapy, the effect of connexins on chemosensitization, the role of apoptotic processes and interactions with the microenvironment. Attempts to restore connexin expression at the transcriptional and post-transcriptional levels are described, as well as promising strategies recently explored. The potential and limitations of the approaches are discussed.


CONCLUSIONS
Connexins have multiple facets, singly, in hemichannel complexes, in gap junctions or interacting with different proteins. The regulation of their expression is not fully resolved and selective manipulation of Cxs expression is therefore a challenge. Although the therapeutic potential of connexins is undeniable, more effort is needed to study the regulation and functions of these proteins.
Kandouz
Mustapha
M
Wayne State University, Department of Pathology, 5101 Cass Avenue, Chemistry Building, Detroit, Michigan 48202, USA. ag1764@wayne.edu
Batist
Gerald
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000378:metabolism; D024201:Bystander Effect / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D018031:Connexin 43 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017630:Connexins / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000502:physiology; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D011499:Protein Processing, Post-Translational / Q000187:drug effects
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018031:Connexin 43; D017630:Connexins; D035683:MicroRNAs