NF-κB in Liver Cancer: The Plot Thickens

Abstract

The role of the NF-kappaB signaling pathway in liver cancer is complex. While some evidence suggests that in the liver, like in many other organ systems, NF-kappaB is oncogenic, there is strong evidence showing that in certain liver cancer models NF-kappaB suppresses tumorigenesis. These contrasting findings cannot be dismissed on technicalities and are likely due to the complex nature of the NF-kappaB response. Similar contrasting findings regarding NF-kappaB activity are revealed in skin cancer models. Thus, it is possible that the contradictory role of NF-kappaB in tumorigenesis is a general phenomenon and not an oddity related solely to the liver. Further studies are indicated to decipher the underlying molecular mechanisms. Revealing these mechanisms may facilitate the identification of patient subgroups and specific situations in which NF-kappaB inhibition will be a preferred therapeutic option. Moreover, it is possible that specific interventions could boost the tumor suppressor functions of NF-kappaB in tumors that harbor mutations that render this pathway constitutively active.