| First Author | Zhang S | Year | 2017 |
| Journal | Cancer Cell | Volume | 31 |
| Issue | 5 | Pages | 669-684.e7 |
| PubMed ID | 28486106 | Mgi Jnum | J:242576 |
| Mgi Id | MGI:5905686 | Doi | 10.1016/j.ccell.2017.04.004 |
| Citation | Zhang S, et al. (2017) Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. Cancer Cell 31(5):669-684.e7 |
| abstractText | Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis. Importantly, the depletion or inactivation of Akt or Skp2 abrogated Hippo signal deficiency-induced liver tumorigenesis, indicating their epistatic interaction. Thus, we conclude that Hippo-Yap signaling suppresses cell polyploidy and oncogenesis through Skp2. |
