Evidence map›Paper›PMID 28486106›Full record

ArticleCancer cell2017

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 and 14 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
9.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

104 citing papers in PubMed, 169 citations in OpenAlex.

  1. Review
  2. RHAMM drives formation of polyploid cancer cells and confers resistance to ER-targeted therapy in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  20. Surviving the Storm: The Role of Poly- and Depolyploidization in Tissues and Tumors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 8 institutions in 4 countries.

Shihao ZhangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Qinghua ChenState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Qingxu LiuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Yuxi LiState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Xiufeng SunState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Lixin HongState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Suyuan JiState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Chengyan LiuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Jing GengState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Weiji ZhangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Zhonglei LuDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Zhen-Yu YinDepartment of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Xiamen, Fujian 361004, China.
Yuanyuan ZengDepartment of Translational Medicine, Medical College of Xiamen University, Xiamen, Fujian 361102, China.
Kwang-Huei LinDepartment of Biochemistry, College of Medicine, Chang Gung University, Liver Research Center, Chang Gung Memorial Hospital, TaoYuan 333, Taiwan, ROC.
Qiao WuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Qiyuan LiDepartment of Translational Medicine, Medical College of Xiamen University, Xiamen, Fujian 361102, China.
Keiko NakayamaDivision of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Keiich I NakayamaDivision of Cell Regulation Systems, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Xianming DengState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Randy L JohnsonDepartment of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Liang ZhuDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Daming GaoKey Laboratory of System Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Lanfen ChenState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: chenlanfen@xmu.edu.cn.
Dawang ZhouState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address: dwzhou@xmu.edu.cn.
Xiamen University · CNAlbert Einstein College of Medicine · USChang Gung University · TWChinese Academy of Sciences · CNKyushu University · JPThe University of Texas MD Anderson Cancer Center · USTohoku University · JPZhongshan Hospital of Xiamen University · CN

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Special Animal CoreP30DK041296 · NIDDK · YESHIVA UNIVERSITY · PI WOLKOFF, ALLAN W · 1989 to 2018
$22.9M
NCI NIH HHS P30 CA016672NIDDK NIH HHS P30 DK041296
6 · The paper itself

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.

Indexed as

Cell ProliferationPloidiesAcetylationAdaptor Proteins, Signal TransducingAnimalsCarcinoma, HepatocellularCell Cycle ProteinsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p27CytosolEpistasis, GeneticFemaleForkhead Transcription FactorsGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHep G2 CellsAdaptor Proteins, Signal TransducingAkt1 protein, mouseCDKN1B protein, humanCdkn1b protein, mouseCell Cycle ProteinsCyclin-Dependent Kinase Inhibitor p27Forkhead Transcription Factorsp300-CBP-Associated Factorp300-CBP Transcription FactorsPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktS-Phase Kinase-Associated ProteinsTranscription FactorsYAP1 protein, humanYap1 protein, mouseYAP-Signaling Proteinsgenomic instabilityHippop27polyploidySkp2tumorigenesisYap

Identifiers

PMID28486106
PMCPMC5863541
OpenAlexW2612971862

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.