Evidence map›Paper›PMID 38951874›Full record

ArticleJournal of translational medicine2024

Senescent endothelial cells promote liver metastasis of uveal melanoma in single-cell resolution.

Liang Ma, Xiaoyu He, Yidian Fu, Shengfang Ge, Zhi Yang

Abstract read
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In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

5 authors.

Liang Ma *Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Xiaoyu He *Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Yidian Fu *Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Shengfang GeDepartment of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. geshengfang@sjtu.edu.cn.
Zhi YangDepartment of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. yangzhiscience@163.com.ORCID 0000-0001-9440-7896

Funding

China Postdoctoral Science Foundation 2022M720091National Natural Science Foundation of China 82200961Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology 2022SKLE-KFKT004the Science and Technology Commission of Shanghai 20DZ2270800
6 · The paper itself

Abstract

backgroundUveal melanoma (UM), the most common adult intraocular tumor, is characterized by high malignancy and poor prognosis in advanced stages. Angiogenesis is critical for UM development, however, not only the role of vascular endothelial dysfunction in UM remains unknown, but also their analysis at the single-cell level has been lacking. A comprehensive analysis is essential to clarify the role of the endothelium in the development of UM.

methodsBy using single-cell RNA transcriptomics data of 11 cases of primary and liver metastasis UM, we analyzed the endothelial cell status. In addition, we analyzed and validated ECs in the in vitro model and collected clinical specimens. Subsequently, we explored the impact of endothelial dysfunction on UM cell migration and explored the mechanisms responsible for the endothelial cell abnormalities and the reasons for their peripheral effects.

resultsUM metastasis has a significantly higher percentage of vascular endothelial cells compared to in situ tumors, and endothelial cells in metastasis show significant senescence. Senescent endothelial cells in metastatic tumors showed significant Krüppel-like factor 4 (KLF4) upregulation, overexpression of KLF4 in normal endothelial cells induced senescence, and knockdown of KLF4 in senescent endothelium inhibited senescence, suggesting that KLF4 is a driver gene for endothelial senescence. KLF4-induced endothelial senescence drove tumor cell migration through a senescence-associated secretory phenotype (SASP), of which the most important component of the effector was CXCL12 (C-X-C motif chemokine ligand 12), and participated in the composition of the immunosuppressive microenvironment.

conclusionThis study provides an undesirable insight of senescent endothelial cells in promoting UM metastasis.

Indexed as

Cell MovementCellular SenescenceEndothelial CellsKruppel-Like Factor 4Liver NeoplasmsMelanomaSingle-Cell AnalysisUveal NeoplasmsCell Line, TumorChemokine CXCL12FemaleGene Expression Regulation, NeoplasticHumansKruppel-Like Transcription FactorsMaleUveal MelanomaChemokine CXCL12CXCL12 protein, humanKLF4 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription FactorsCellular senescenceEndothelial dysfunctionKLF4Single cell RNA-seqUveal melanoma

Identifiers

PMID38951874
PMCPMC11218175

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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.