The hallmarks of CDKN1C (p57, KIP2) in cancer

Cyclin-dependent kinase inhibitor 1C CDKN1C (p57KIP2) regulates several hallmarks of cancer, including apoptosis, cell invasion and metastasis, tumor differentiation and angiogenesis. p57KIP2 is generally not mutated in cancer, but its expression is downregulated through epigenetic changes such as DNA methylation and repressive histone marks at the promoter. This opens up possibilities for therapeutic intervention through reactivation of p57KIP2 gene expression. Furthermore, p57KIP2 has been tested as a prognostic factor for many types of cancer, even differentiating between early and late stage cancer. In this review, the multifunctional tumor suppressor capabilities of p57KIP2, the mechanisms of p57KIP2 transcriptional repression in cancer, and the therapeutic potential of reactivation of p57KIP2 protein expression will be discussed.