The pro- and anti-tumoral properties of gap junctions in cancer and their role in therapeutic strategies
Maria C. Oliveira,
Hanne Verswyvel,
Evelien Smits,
Rodrigo M. Cordeiro,
Annemie Bogaerts,
Abraham Lin
Affiliations
Maria C. Oliveira
Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT), Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium; Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580, Santo André, SP, Brazil; Corresponding author. Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT), Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.
Hanne Verswyvel
Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT), Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium
Evelien Smits
Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium
Rodrigo M. Cordeiro
Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, CEP 09210-580, Santo André, SP, Brazil
Annemie Bogaerts
Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT), Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
Abraham Lin
Plasma Lab for Applications in Sustainability and Medicine-Antwerp (PLASMANT), Department of Chemistry, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium; Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Universiteitsplein 1, B-2610, Antwerp, Belgium
Gap junctions (GJs), essential structures for cell-cell communication, are made of two hemichannels (commonly called connexons), one on each adjacent cell. Found in almost all cells, GJs play a pivotal role in many physiological and cellular processes, and have even been linked to the progression of diseases, such as cancer. Modulation of GJs is under investigation as a therapeutic strategy to kill tumor cells. Furthermore, GJs have also been studied for their key role in activating anti-cancer immunity and propagating radiation- and oxidative stress-induced cell death to neighboring cells, a process known as the bystander effect. While, gap junction (GJ)-based therapeutic strategies are being developed, one major challenge has been the paradoxical role of GJs in both tumor progression and suppression, based on GJ composition, cancer factors, and tumoral context. Therefore, understanding the mechanisms of action, regulation, and the dual characteristics of GJs in cancer is critical for developing effective therapeutics. In this review, we provide an overview of the current understanding of GJs structure, function, and paradoxical pro- and anti-tumoral role in cancer. We also discuss the treatment strategies to target these GJs properties for anti-cancer responses, via modulation of GJ function.
