Abstract
Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels. They participate in intercellular communication or communication between the intracellular and extracellular environments. Connexins affect cell homeostasis, growth and differentiation by enabling the exchange of metabolites or by interfering with various signalling pathways. Alterations in the functionality and the expression of connexins have been linked to the occurrence of many diseases. Connexins have been already linked to cancers, cardiac and brain disorders, chronic lung and kidney conditions and wound healing processes. Connexins have been shown either to suppress cancer tumour growth or to increase tumorigenicity by promoting cancer cell growth, migration and invasiveness. A better understanding of the complexity of cancer biology related to connexins and intercellular communication could result in the design of novel therapeutic strategies. The modulation of connexin expression may be an effective therapeutic approach in some types of cancers. Therefore, one important challenge is the search for mechanisms and new drugs, selectively modulating the expression of various connexin isoforms. We performed a systematic literature search up to February 2020 in the electronic databases PubMed and EMBASE. Our search terms were as follows: connexins, hemichannels, cancer and cancer treatment. This review aims to provide information about the role of connexins and gap junctions in cancer, as well as to discuss possible therapeutic options that are currently being studied.
Highlights
Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels [1,2]
This review provides an overview of the role of Cx in cancer pathogenesis and progression and as possible targets for cancer treatment
Gap junctions and hemichannels formed by connexins are responsible for cell–cell communication, the passage of small molecules between contacting cells and between cells and the extracellular milieu
Summary
Connexins (Cx) are members of a protein family that forms intercellular channels localised in gap junction (GJ) plaques and single transmembrane channels called hemichannels [1,2]. Five sub-families are described: GJA, GJB, GJC, GJD and GJE This division is based on the structural similarity of genes, their homology and sequence as well as the length of the connexin cytoplasmic domain [4]. Connexins occur both in the form of cell-to-cell plasma membrane domains known as gap junctions (GJ) and single-membrane hemichannels [1]. Connexins may be involved in alteration of intracellular communication, can interfere with signalling pathways or modulate cells by autocrine and paracrine mechanisms. This review provides an overview of the role of Cx in cancer pathogenesis and progression and as possible targets for cancer treatment
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