Connexins: junctional and non-junctional modulators of proliferation

Mounting evidence indicates that dysregulation of gap junctions and their structural subunits-connexins-often occurs in, and sometimes causes, a variety of proliferative disorders, including cancer. Connexin-mediated regulation of cell proliferation is complex and may involve modulation of gap junction intercellular communication (GJIC), hemichannel signalling, or gap junction-independent paths. However, the exact mechanisms linking connexins to proliferation remain poorly defined and a number of contradictory studies report both pro-and anti-proliferative effects, effects that often depend on the cell or tissue type or the microenvironment. The present review covers junctional and non-junctional regulation of proliferation by connexins, with a particular emphasis on their association with cancer.