The role of connexins in prostate cancer promotion and progression.

Prostate cancer is a prevalent disease that is characterized by a presumably long latency period and a moderate propensity to metastasize. Although a range of mechanisms have been implicated in prostate carcinogenesis, the factors determining the initiation of metastasis remain obscure. The synchronized function of prostate cells depends on their metabolic and electrical coupling; disturbance of these functions has long been suggested to be integral to prostate carcinogenesis. However, although connexins form intercellular channels involved in gap-junction-mediated intercellular coupling (GJIC), whether these proteins also have GJIC-independent roles in cancer progression and metastasis remains a matter of debate. Some data indicate a correlation between connexin expression and the invasive potential of prostate cancer cells, which points to stage-specific functions of connexins during prostate cancer development. For example, restoration of connexin expression seems to be crucial for the formation of invasive cell subsets within heterogeneous prostate cancer cell populations that have undergone aberrant differentiation. Consequently, the clinical application of therapeutic and prophylactic approaches focused on the modulation of connexin expression in prostate cancer cells should be reconsidered.