The alternative NF-κB activation pathway and cancer : friend or foe?

The family of NF-kappa B transcription factors plays a key role in diverse biological processes, such as inflammatory and immune responses, cell survival and tumor development. A new NF-kappa B activation pathway has been recently uncovered, the so-called alternative NF-kappa B activation pathway. It has been shown that this pathway mainly controls the activity of ReIB, a member of the NF-kappa B family, and its activation requires IKK alpha, one of the two catalytic subunits of the IKK complex. Recent studies suggest that constitutive activation of the alternative pathway may be involved in tumor development, but most surprisingly it is also reported that IKK alpha exerts a protective function against uncontrolled cell proliferation and cancer development. This review discusses recent progresses in the understanding on how the alternative pathway may participate in cancer development, focusing more specifically on ReIB and IKK alpha.