Connexin 43 (Cx43) in cancer: Implications for therapeutic approaches via gap junctions

Gap junctions are membrane channels found in all cells of the human body that are essential to cellular physiology. Gap junctions are formed from connexin proteins and are responsible for transfer of biologically active molecules, metabolites, and salts between neighboring cells or cells and their extracellular environment. Over the last few years, aberrant connexin 43 (Cx43) expression has been associated with cancer recurrence, metastatic spread, and poor survival. Here we provide an overview of the general structure and function of gap junctions and review their roles in different cancer types. We discuss new therapeutic approaches targeting Cx43 and potential new ways of exploiting gap junction transfer for drug delivery and anti-cancer treatment. The permeability of Cx43 channels to small molecules and macromolecules makes them highly attractive targets for delivering drugs directly into the cytoplasm. Cancer cells overexpressing Cx43 may be more permeable and sensitive to chemotherapeutics. Because Cx43 can either act as a tumor suppressor or oncogene, biomarker analysis and a better understanding of how Cx43 contextually mediates cancer phenotypes will be required to develop clinically viable Cx43-based therapies.