Understanding p27kip1 Deregulation in Cancer: Downregulation or Mislocalizaiton?

There is considerable evidence that the inactivation of the cyclin-dependent kinase inhibitor p27kip1 is a fundamental step for the development of human malignancies. In particular, reduced expression of p27kip1, due to increased protein degradation, correlates with poor prognosis of patients affected by various types of cancer. The purpose of this mini-review is to present an overview of the current understanding of the alteration of p27kip1 function in human cancer and to describe the different mechanisms that contributes to it. Particular emphasis is placed on the novel finding of p27kip1 mislocalization in tumor cells and on the biochemical pathways responsible for p27kip1 cytosolic accumulation. Finally, we review the possible clinical implications of these observations with respect to prognosis and novel anticancer therapies.