Increased Expression of NPM1 Suppresses p27^Kip1 Function in Cancer Cells

• Main Authors: Tatsuya Kometani, Takuya Arai, Taku Chibazakura
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Cancers
• Subjects: p27^Kip1; nucleophosmin isoform 1; cell proliferation; CDK inhibitor; cancer cells; protein–protein interaction
• Online Access: https://www.mdpi.com/2072-6694/12/10/2886

p27^Kip1, a major cyclin-dependent kinase inhibitor, is frequently expressed at low levels in cancers, which correlates with their malignancy. However, in this study, we found a qualitative suppression of p27 overexpressed in some cancer cells. By proteomic screening for factors interacting with p27, we identified nucleophosmin isoform 1 (NPM1) as a novel p27-interacting factor and observed that NPM1 protein was expressed at high levels in some cancer cells. NPM1 overexpression in normal cells suppressed p27 function, and conversely, NPM1 knockdown in cancer cells restored the function in vitro. Furthermore, the tumors derived from cancer cells carrying the combination of p27 overexpression and NPM1 knockdown constructs showed significant suppression of growth as compared with those carrying other combinations in mouse xenograft models. These results strongly suggest that increased expression of NPM1 qualitatively suppresses p27 function in cancer cells.