Yin Yang 1 and Raf-1 Kinase Inhibitory Protein Status in Hepatocellular Carcinoma: Future Perspectives

Abstract

We focus on to the role of the transcription factors NF-κB and Yin Yang 1 (YY1) and of Raf-1 kinase inhibitory protein (RKIP) in hepatocellular carcinoma (HCC). YY1, whose expression is enhanced by NF-κB, favors tumorigenesis. RKIP inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist and there is separate evidence that relevant increases in YY1 and reductions in RKIP occur in HCC. In a recent study on clinical HCC, we found that, indeed, the ratio of YY1 to RKIP mRNA and protein expression is very frequently profoundly inverted in tumors compared with adjacent tissues. Hyperactivation of YY1 in tumors was corroborated by its nuclear localization and by concomitant increases in the coactivator YY1AP. Overall, the alteration in the YY1-RKIP balance might represent, beside a marker of malignant progression, a target of therapeutic interventions in HCC, which will include application of NF-κB inhibitors, also in conjunction with the active agent sorafenib