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

40 引用 (Scopus)

抄録

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

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Polyploidy
Ploidies
Carcinogenesis
Cyclin-Dependent Kinase Inhibitor p27
Ubiquitin-Protein Ligases
Genomic Instability
Aneuploidy
Acetylation
Diploidy
Cell Division
Cytosol
Liver
Growth

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

Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. / Zhang, Shihao; Chen, Qinghua; Liu, Qingxu; Li, Yuxi; Sun, Xiufeng; Hong, Lixin; Ji, Suyuan; Liu, Chengyan; Geng, Jing; Zhang, Weiji; Lu, Zhonglei; Yin, Zhen Yu; Zeng, Yuanyuan; Lin, Kwang Huei; Wu, Qiao; Li, Qiyuan; Nakayama, Keiko; Nakayama, Keiich I.; Deng, Xianming; Johnson, Randy L.; Zhu, Liang; Gao, Daming; Chen, Lanfen; Zhou, Dawang.

:: Cancer Cell, 巻 31, 番号 5, 08.05.2017, p. 669-684.e7.

研究成果: ジャーナルへの寄稿記事

Zhang, S, Chen, Q, Liu, Q, Li, Y, Sun, X, Hong, L, Ji, S, Liu, C, Geng, J, Zhang, W, Lu, Z, Yin, ZY, Zeng, Y, Lin, KH, Wu, Q, Li, Q, Nakayama, K, Nakayama, KI, Deng, X, Johnson, RL, Zhu, L, Gao, D, Chen, L & Zhou, D 2017, 'Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2', Cancer Cell, 巻. 31, 番号 5, pp. 669-684.e7. https://doi.org/10.1016/j.ccell.2017.04.004
Zhang S, Chen Q, Liu Q, Li Y, Sun X, Hong L その他. Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. Cancer Cell. 2017 5 8;31(5):669-684.e7. https://doi.org/10.1016/j.ccell.2017.04.004
Zhang, Shihao ; Chen, Qinghua ; Liu, Qingxu ; Li, Yuxi ; Sun, Xiufeng ; Hong, Lixin ; Ji, Suyuan ; Liu, Chengyan ; Geng, Jing ; Zhang, Weiji ; Lu, Zhonglei ; Yin, Zhen Yu ; Zeng, Yuanyuan ; Lin, Kwang Huei ; Wu, Qiao ; Li, Qiyuan ; Nakayama, Keiko ; Nakayama, Keiich I. ; Deng, Xianming ; Johnson, Randy L. ; Zhu, Liang ; Gao, Daming ; Chen, Lanfen ; Zhou, Dawang. / Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2. :: Cancer Cell. 2017 ; 巻 31, 番号 5. pp. 669-684.e7.
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abstract = "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.",
author = "Shihao Zhang and Qinghua Chen and Qingxu Liu and Yuxi Li and Xiufeng Sun and Lixin Hong and Suyuan Ji and Chengyan Liu and Jing Geng and Weiji Zhang and Zhonglei Lu and Yin, {Zhen Yu} and Yuanyuan Zeng and Lin, {Kwang Huei} and Qiao Wu and Qiyuan Li and Keiko Nakayama and Nakayama, {Keiich I.} and Xianming Deng and Johnson, {Randy L.} and Liang Zhu and Daming Gao and Lanfen Chen and Dawang Zhou",
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T1 - Hippo Signaling Suppresses Cell Ploidy and Tumorigenesis through Skp2

AU - Zhang, Shihao

AU - Chen, Qinghua

AU - Liu, Qingxu

AU - Li, Yuxi

AU - Sun, Xiufeng

AU - Hong, Lixin

AU - Ji, Suyuan

AU - Liu, Chengyan

AU - Geng, Jing

AU - Zhang, Weiji

AU - Lu, Zhonglei

AU - Yin, Zhen Yu

AU - Zeng, Yuanyuan

AU - Lin, Kwang Huei

AU - Wu, Qiao

AU - Li, Qiyuan

AU - Nakayama, Keiko

AU - Nakayama, Keiich I.

AU - Deng, Xianming

AU - Johnson, Randy L.

AU - Zhu, Liang

AU - Gao, Daming

AU - Chen, Lanfen

AU - Zhou, Dawang

PY - 2017/5/8

Y1 - 2017/5/8

N2 - 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.

AB - 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.

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