Evidence map›Paper›PMID 31212215›Full record

ArticleRedox biology2019

Hippo kinases regulate cell junctions to inhibit tumor metastasis in response to oxidative stress.

Yang Wang, Juan Li, Ya Gao, Yue Luo, Hong Luo, Liang Wang, Yong Yi, Zengqiang Yuan, Zhi-Xiong Jim Xiao

Open access · goldAbstract read
In one paragraph

Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 44 citations in OpenAlex.

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  18. The dual role of p63 in cancer.Frontiers in oncology · 2023
    Review
  19. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Yang WangCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Juan LiCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Ya GaoCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Yue LuoCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Hong LuoCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Liang WangCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Yong YiCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China.
Zengqiang YuanInstitute of Basic Medical Sciences, AMMS, Beijing, 100850, China.
Zhi-Xiong Jim XiaoCenter of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, 610064, China; Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA. Electronic address: jimzx@scu.edu.cn.
Sichuan University · CNInstitute of Basic Medical Sciences of the Chinese Academy of Medical Sciences

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reactive oxygen species (ROS) are key regulators in cell proliferation, survival, tumor initiation and development. However, the role of ROS in tumor metastasis is less clear. Here, we show that oxidative stress inhibited tumor metastasis via activation of Hippo kinase MST1/2, which led to the phosphorylation and nuclear accumulation of FoxO3a, resulting in upregulation of ΔNp63α expression and suppression of cell migration independent of YAP. Strikingly, while loss of MST1 led to and disruption of cell-cell junction exemplified by reduced E-cadherin expression, resulting in scattered cell growth, loss of MST2 led to disruption of cell-matrix adhesion as evidenced by reduced integrin β4, resulting in increased cell migration and tumor metastasis. Furthermore, expression of MST1 and MST2 was down-regulated in human breast carcinoma. Furthermore, oxidative stress inhibited HER2-or PI3K-mediated tumor metastasis via the MST2-FoxO3a-ΔNp63α pathway. Together, these results that this noncanonical Hippo MST2-FoxO3a-ΔNp63α pathway may play a critical role in ROS-mediated regulation of cell migration and tumor metastasis.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsAntigens, CDBreast NeoplasmsCadherinsCell Line, TumorCell MovementCell ProliferationEpithelial CellsErb-b2 Receptor Tyrosine KinasesFemaleForkhead Box Protein O3Hippo KinasesHumansHydrogen PeroxideIntegrin beta4Antigens, CDCadherinsCDH1 protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesForkhead Box Protein O3FOXO3 protein, humanHippo KinasesHydrogen PeroxideIntegrin beta4Intracellular Signaling Peptides and ProteinsITGB4 protein, humanPhosphatidylinositol 3-KinaseProtein Serine-Threonine KinasesReactive Oxygen SpeciesSerine-Threonine Kinase 3STK3 protein, humanSTK4 protein, humanTP63 protein, humanTranscription FactorsTumor Suppressor ProteinsCell-cell junctionCell-matrix adhesionHippo kinaseMetastasisΔNp63α

Identifiers

PMID31212215
PMCPMC6582208
OpenAlexW2948913519

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.