Colon carcinogenesis: Learning from NF-kappaB and AP-1.

Colorectal cancer (CRC) is among the most common types of cancer attributed to genetic alterations. Its manifestation implicates NF-kappaB and AP-1 signaling pathways by virtue of their regulative role on the genetic control of cell cycle and apoptosis as well as by their capacity to be constitutively activated or exogenously induced by growth factors, cytokines, stress signals and oncoproteins. In CRC, the positive impact of NF-kappaB and AP-1 on the transcription of angiogenic and invasive factors strongly implicates these transcription factors in the transition of benign carcinomas towards a metastatic phenotype. Furthermore, the deregulated function of NF-kappaB and AP-1 in CRC cells affects inflammatory cascades, manifested by the ample production of inflammatory mediators. In this perspective, inhibition of NF-kappaB and AP-1 signaling mechanisms has become a rational target in the development of novel therapeutic approaches against CRC. Copyright 2010 Elsevier Ltd. All rights reserved.