Gap junctions and tumour progression.

Abstract

Gap junctional intercellular communication has been implicated in growth control and differentiation. The mechanisms by which connexins, the gap junction proteins, act as tumor suppressors are unclear. In this review, several different mechanisms are considered. Since transformation results in a loss of the differentiated state, one mechanism by which gap junctions may control tumour progression is to promote or enhance differentiation. Processes of differentiation and growth control are mediated at the genetic level. Thus, an alternative or complimentary mechanism of tumour suppression could involve the regulation of gene expression by connexins and gap junctional coupling. Finally, gap junction channels form a conduit between cells for the exchange of ions, second messengers, and small metabolites. It is clear that the sharing of these molecules can be rather selective and may be involved in growth control processes. In this review, examples will be discussed that provide evidence for each of these mechanisms. Taken together, these findings point to a variety of mechanims by which connexins and the gap junction channels that they form may control tumour progression.