ABSTRACT
It is now well accepted that the NF-kappa B pathways are involved in inflammatory diseases, cancer development and progression in human solid tumors. The NF-kappa B signaling element I kappa B alpha was shown to inactivates NF-kappa B activity through sequestration of this transcription factor in the cytoplasm. In the present study, we investigated the impact of the I kappa B alpha on the invasive growth of human colon cancer cells HCT8/S11 stably transfected by this endogenous NF-kappa B inhibitor. We report that I kappa B alpha ectopic expression inhibited NF-kappa B promoter activity induced by the Y527Fsrc oncogene, and reduced HCT8/S11 cell migration in wound healing assays. Our data show that I kappa B alpha abrogated collagen type I invasion induced by the trefoil factors TFF1 and TFF3, but was ineffective on the invasive phenotype determined by leptin. Moreover, I kappa B alpha reduced HCT8/S11 cell proliferation in vitro and the growth of their corresponding tumor xenografts established in the athymic mice. Taken together our data demonstrated that the intrinsic NF-kappa B inhibitor I kappa B alpha negates several transforming functions in human colon cancer cells. Our data provide the rationale for further preclinical and clinical studies based on therapeutic interventions targeting NF-kappa B pathway