Cell autonomous and non-autonomous functions of IKKβ and NF-κb during the pathogenesis of gastrointestinal tumors

Abstract

Genetic studies describing a link between cancer and inflammation have increased recently. Activation of the transcription factor nuclear factor-κB (NF-κB) and its effector pathways has been proposed to be the missing link between these two processes. NF-κB is persistently activated in several types of tumors. However, NF-κB has a distinct role in cancer cells and in inflammatory cells. While in tumor cells NF-κB controls cell survival, in inflammatory cells NF-κB activates genes that encode pro-inflammatory cytokines which further act in a paracrine manner within the tumor microenvironment to contribute to tumorigenesis. Inactivation of NF-κB can also reduce chemore sistance and radioresistance of cancer cells. Therefore, specific NF-κB inhibition in combination with cytotoxic drugs and/or irradiation represents a very promising strategy for cancer therapy. © 2011 by the authors; licensee MDPI, Basel, Switzerland.