Gap junctions composed of
connexin (Cx), a large
protein family with a number of subtypes, are a main apparatus to maintain cellular homeostasis in many organs. Gap junctional intercellular communication (GJIC) is actively involved in all aspects of the cellular life cycle, ranging from cell growth to cell death. It is also known that the Cx gene acts as a
tumor-suppressor due to the maintenance of cellular homeostasis via GJIC. In addition to this function, recent data show that the GJIC-independent function of Cx gene contributes to the
tumor-suppressive effect of the gene with specificity to certain cells. With respect to the
tumor-suppressive effects, Cx genes acts as
tumor-suppressors in primary
cancers, but the effects are still conflicting in invasive and metastatic
cancers. We have previously reported that Cx32 is specifically downregulated in human
renal cell carcinoma (RCC) cell lines as well as cancerous regions when compared to normal regions in kidneys. In recent studies, we have also reported that Cx32 suppresses growth, invasion and
metastasis of RCC cells. In this minireview, we refer to a new aspect of Cx32-dependent functions against cell proliferation, invasion and
metastasis in RCC cells, especially in a GJIC-independent manner.