Evidence map›Paper›PMID 29035390›Full record

ArticleOncogene2018

Epigenetic silencing of the dual-role signal mediator, ANGPTL4 in tumor tissues and its overexpression in the urothelial carcinoma microenvironment.

H-Y Hsieh, Y-C Jou, C-L Tung, Y-S Tsai, Y-H Wang, C-L Chi, R-I Lin, S-K Hung, Y-M Chuang, S-F Wu and 4 more

Abstract read
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In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

26 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  7. Dual role of ANGPTL4 in inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Review
  8. Article
  9. Guidelines on lung adenocarcinoma prognosis based on immuno-glycolysis-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
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  11. Article
  12. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 1 country.

H-Y HsiehDepartment of Medical Research, Ditmanson Medical Fountain Chiayi Christian Hospital, Chiayi, Taiwan.
Y-C JouDepartment of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
C-L TungDepartment of Pathology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
Y-S TsaiDepartment of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Y-H WangGraduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
C-L ChiDepartment of Pathology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan.
R-I LinDepartment of Radiation Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan.
S-K HungDepartment of Radiation Oncology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan.
Y-M ChuangDepartment of Life Science, National Chung Cheng University, Chiayi, Taiwan.
S-F WuDepartment of Life Science, National Chung Cheng University, Chiayi, Taiwan.
C LiDepartment of Life Science, National Chung Cheng University, Chiayi, Taiwan.
C-H ShenDepartment of Urology, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
M W Y ChanDepartment of Life Science, National Chung Cheng University, Chiayi, Taiwan.
C-D HsuDepartment of Medical Research, Ditmanson Medical Fountain Chiayi Christian Hospital, Chiayi, Taiwan.
National Chung Cheng University · TWChia-Yi Christian Hospital · TWBuddhist Tzu Chi General Hospital · TWNational Cheng Kung University Hospital · TWTaipei Medical University · TWTzu Chi University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear. In this study, using methylation-specific PCR and bisulfite pyrosequencing, we show that ANGPTL4 is transcriptionally repressed by DNA methylation in UC cell lines and primary tumor samples, as compared with adjacent noncancerous bladder epithelium. Functional studies further demonstrated that ectopic expression of ANGPTL4 potently suppressed UC cell proliferation, monolayer colony formation in vitro, and invasion, migration, and xenograft formation in vivo. Surprisingly, circulating ANGPTL4 was significantly higher in plasma samples from UC patients than normal control, suggesting it might be secreted from other cell types. Interestingly, our data also indicated that exogenous cANGPTL4 could promote cell proliferation and cell migration via activation of signaling through the Erk/focal adhesion kinase axis. We further confirmed that mouse xenograft tumor growth could be promoted by administration of exogenous cANGPTL4. Finally, immunohistochemistry demonstrated that ANGPTL4 was downregulated in tumor cells but overexpressed in tumor adjacent stromal tissues of muscle-invasive UC tissue samples. In conclusion, our data support dual roles for ANGPTL4 in UC progression, either as a tumor suppressor or oncogene, in response to microenvironmental context.

Indexed as

Tumor MicroenvironmentAgedAged, 80 and overAngiopoietin-Like Protein 4AnimalsCarcinogenesisCarcinoma, Transitional CellCase-Control StudiesCell Line, TumorCell MovementCell ProliferationCystectomyDNA MethylationDown-RegulationEpigenesis, GeneticFemaleAngiopoietin-Like Protein 4ANGPTL4 protein, human

Identifiers

PMID29035390
OpenAlexW2766199426

What OpenQuestion holds

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Registered trials

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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.