Evidence map›Paper›PMID 30783090›Full record

ArticleNature communications2019

A MST1-FOXO1 cascade establishes endothelial tip cell polarity and facilitates sprouting angiogenesis.

Yoo Hyung Kim, Jeongwoon Choi, Myung Jin Yang, Seon Pyo Hong, Choong-Kun Lee, Yoshiaki Kubota, Dae-Sik Lim, Gou Young Koh

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

54 citing papers in PubMed, 102 citations in OpenAlex.

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  12. EndothelialFrontiers in cell and developmental biology · 2025
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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

8 authors at 3 institutions in 2 countries.

Yoo Hyung KimGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.ORCID http://orcid.org/0000-0002-5923-4915
Jeongwoon ChoiBiomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, 34141, Korea.
Myung Jin YangBiomedical Science and Engineering Interdisciplinary Program, KAIST, Daejeon, 34141, Korea.
Seon Pyo HongCenter for Vascular Research, Institute for Basic Science (IBS), Daejeon, 34141, Korea.
Choong-Kun LeeGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea.
Yoshiaki KubotaDepartment of Vascular Biology, The Sakaguchi Laboratory, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Dae-Sik LimNational Creative Research Initiatives Center for Cell Division and Differentiation, Department of Biological Science, KAIST, Daejeon, 34141, Korea.
Gou Young KohGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Korea. gykoh@kaist.ac.kr.ORCID http://orcid.org/0000-0002-1231-1485
Korea Advanced Institute of Science and Technology · KRInstitute for Basic Science · KRKeio University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hypoxia is a main driver of sprouting angiogenesis, but how tip endothelial cells are directed to hypoxic regions remains poorly understood. Here, we show that an endothelial MST1-FOXO1 cascade is essential for directional migration of tip cells towards hypoxic regions. In mice, endothelial-specific deletion of either MST1 or FOXO1 leads to the loss of tip cell polarity and subsequent impairment of sprouting angiogenesis. Mechanistically, MST1 is activated by reactive oxygen species (ROS) produced in mitochondria in response to hypoxia, and activated MST1 promotes the nuclear import of FOXO1, thus augmenting its transcriptional regulation of polarity and migration-associated genes. Furthermore, endothelial MST1-FOXO1 cascade is required for revascularization and neovascularization in the oxygen-induced retinopathy model. Together, the results of our study delineate a crucial coupling between extracellular hypoxia and an intracellular ROS-MST1-FOXO1 cascade in establishing endothelial tip cell polarity during sprouting angiogenesis.

Indexed as

Active Transport, Cell NucleusAnimalsCell HypoxiaCell PolarityCells, CulturedEndothelial CellsForkhead Box Protein O1Gene Expression RegulationHepatocyte Growth FactorHippo KinasesHumansHuman Umbilical Vein Endothelial CellsIntracellular Signaling Peptides and ProteinsMice, Inbred C57BLMice, Mutant StrainsNeovascularization, PathologicForkhead Box Protein O1FOXO1 protein, humanFoxo1 protein, mouseHepatocyte Growth FactorHippo KinasesIntracellular Signaling Peptides and ProteinsLats1 protein, mouseProtein Serine-Threonine KinasesProto-Oncogene ProteinsReactive Oxygen SpeciesSTK4 protein, humanStk4 protein, mouse

Identifiers

PMID30783090
PMCPMC6381131
OpenAlexW2917327798

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.