Connexin 43 expression promotes malignancy of HuH7 hepatocellular carcinoma cells via the inhibition of cell–cell communication

In normal liver, Connexin (Cx) 43 is not detected, but up-regulated in some liver cancers. We herein investigated the role of Cx43 in hepatoma cell carcinogenesis. Cx43-silenced HuH7 cells using shRNA showed lower growth and higher differentiation, and Cx43-overexpressing cells exhibited rapid growth and low differentiation. Unexpectedly, gap junctional intercellular communication (GJIC) was inversely correlated with Cx43 levels. Furthermore, the expression level and promoter activity of Cx32 was negatively regulated by the expression of Cx43. From these data, Cx43 expression may be in part responsible for the malignancy of hepatoma cells through a decrease in GJIC composed of Cx32.