Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2

Shihao Zhang, Qinghua Chen, Qingxu Liu, Yuxi Li, Xiufeng Sun, Lixin Hong, Suyuan Ji, Chengyan Liu, Jing Geng, Weiji Zhang, Zhonglei Lu, Zhen Yu Yin, Yuanyuan Zeng, Kwang Huei Lin, Qiao Wu, Qiyuan Li, Keiko Nakayama, Keiich I. Nakayama, Xianming Deng, Randy L. JohnsonLiang Zhu, Daming Gao, Lanfen Chen, Dawang Zhou

研究成果: ジャーナルへの寄稿記事

51 引用 (Scopus)

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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.

元の言語英語
ページ(範囲)669-684.e7
ジャーナルCancer Cell
31
発行部数5
DOI
出版物ステータス出版済み - 5 8 2017

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

これを引用

Zhang, S., Chen, Q., Liu, Q., Li, Y., Sun, X., Hong, L., ... Zhou, D. (2017). Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. Cancer Cell, 31(5), 669-684.e7. https://doi.org/10.1016/j.ccell.2017.04.004