Evidence map›Paper›PMID 32005975›Full record

ArticleOncogene2020

C1GALT1 is associated with poor survival and promotes soluble Ephrin A1-mediated cell migration through activation of EPHA2 in gastric cancer.

Po-Chu Lee, Syue-Ting Chen, Ting-Chun Kuo, Tzu-Chi Lin, Mei-Chun Lin, John Huang, Ji-Shiang Hung, Chia-Lang Hsu, Hsueh-Fen Juan, Po-Huang Lee and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.8field-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

37 citing papers in PubMed, 59 citations in OpenAlex.

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  7. Eph receptor signaling complexes in the plasma membrane.Trends in biochemical sciences · 2024
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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

11 authors at 2 institutions in 1 country.

Po-Chu LeeDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-5486-6841
Syue-Ting ChenGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ting-Chun KuoDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Tzu-Chi LinGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Mei-Chun LinDepartment of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
John HuangDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Ji-Shiang HungDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Chia-Lang HsuDepartment of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.ORCID http://orcid.org/0000-0002-7447-8045
Hsueh-Fen JuanDepartment of Life Science, National Taiwan University, Taipei, Taiwan.ORCID http://orcid.org/0000-0003-4876-3309
Po-Huang LeeDepartment of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Min-Chuan HuangGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan. mchuang@ntu.edu.tw.
National Taiwan University · TWNational Taiwan University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

C1GALT1 controls the crucial step of GalNAc-type O-glycosylation and is associated with both physiologic and pathologic conditions, including cancers. EPH receptors comprise the largest family of receptor tyrosine kinases (RTKs) and modulate a diverse range of developmental processes and human diseases. However, the role of C1GALT1 in the signaling of EPH receptors remains largely overlooked. Here, we showed that C1GALT1 high expression in gastric adenocarcinomas correlated with adverse clinicopathologic features and is an independent prognostic factor for poor overall survival. Silencing or loss of C1GALT1 inhibited cell viability, migration, invasion, tumor growth and metastasis, as well as increased apoptosis and cytotoxicity of 5-fluorouracil in AGS and MKN45 cells. Phospho-RTK array and western blot analysis showed that C1GALT1 depletion suppressed tyrosine phosphorylation of EPHA2 induced by soluble Ephrin A1-Fc. O-glycans on EPHA2 were modified by C1GALT1 and both S277A and T429A mutants, which are O-glycosites on EPHA2, dramatically enhanced phosphorylation of Y588, suggesting that not only overall O-glycan structures but also site-specific O-glycosylation can regulate EPHA2 activity. Furthermore, depletion of C1GALT1 decreased Ephrin A1-Fc induced migration and reduced Ephrin A1 binding to cell surfaces. The effects of C1GALT1 knockdown or knockout on cell invasiveness in vitro and in vivo were phenocopied by EPHA2 knockdown in gastric cancer cells. These results suggest that C1GALT1 promotes phosphorylation of EPHA2 and enhances soluble Ephrin A1-mediated migration primarily by modifying EPHA2 O-glycosylation. Our study highlights the importance of GalNAc-type O-glycosylation in EPH receptor-regulated diseases and identifies C1GALT1 as a potential therapeutic target for gastric cancer.

Indexed as

AcetylgalactosamineAdenocarcinomaAnimalsCell Line, TumorCell MovementCell SurvivalEphrin-A1Ephrin-A2GalactosyltransferasesGene Expression Regulation, NeoplasticGene Knockdown TechniquesGene Knockout TechniquesGlycosylationHumansKaplan-Meier EstimateMaleAcetylgalactosamineC1GALT1 protein, humanEFNA1 protein, humanEPHA2 protein, humanEphrin-A1Ephrin-A2GalactosyltransferasesReceptor, EphA2

Identifiers

PMID32005975
PMCPMC7098884
OpenAlexW3003986515

What OpenQuestion holds

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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.