Evidence map›Paper›PMID 31286874›Full record

ArticleBMC cancer2019

RNF43 ubiquitinates and degrades phosphorylated E-cadherin by c-Src to facilitate epithelial-mesenchymal transition in lung adenocarcinoma.

Yunfeng Zhang, Liangzhang Sun, Xiao Gao, Aining Guo, Yan Diao, Yang Zhao

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

21 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Yunfeng ZhangSecond Thoracic Department, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004.
Liangzhang SunThoracic Department, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004.
Xiao GaoDepartment of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004.
Aining GuoDepartment of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004.
Yan DiaoDepartment of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004.
Yang ZhaoDepartment of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China, 710004. szhaoy@126.com.
Second Affiliated Hospital of Xi'an Jiaotong University · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

National Natural Science Foundation of China 81301847National Natural Science Foundation of China 81872390
6 · The paper itself

Abstract

backgroundIn epithelial cells, tyrosine kinases induce tyrosine phosphorylation and ubiquitination of the E-cadherin complex, which is responsible for the epithelial-mesenchymal transition (EMT). However, the precise mechanisms remain unclear.

methodsProtein antibody microarray analysis and E3 ligase profiling were performed to detect the unique E3 ligase underlying E-cadherin downregulation in lung adenocarcinoma tissues. Gene knockdown was performed using viral shRNA. Immunoblotting, immunofluorescence, immunoprecipitation, and xenograft models in vivo were integratively applied to explore RNF43-induced EMT in lung adenocarcinoma cell lines.

resultsProtein antibody microarray analysis and E3 ligase profiling revealed that the RING finger protein 43 (RNF43) was linked to E-cadherin downregulation within the context of c-Src activation in lung adenocarcinoma tissues. In addition, the c-Src-Caspase-8 interaction markedly increased c-Src activity. Activated c-Src phosphorylated E-cadherin at the tyrosine 797 site to initiate RNF43-mediated E-cadherin ubiquitination at lysine 816 and subsequent degradation, thus allowing the nuclear translocation of β-catenin and upregulation of Vimentin and RNF43 expression in lung adenocarcinoma cells. Decreased E-cadherin expression and increased Vimentin expression induced the EMT phenotype and promoted tumor metastasis. The Frizzled 8 (Frz8)-RNF43-induced ubiquitination of phosphorylated E-cadherin was blocked by a monoclonal antibody against the cysteine-rich domain (CRD) of Frz8 but not by antibodies against the protease domain (PA) of RNF43.

conclusionsOur data suggest that RNF43 participates in the regulation of EMT in the metastasis of lung adenocarcinoma through the ubiquitination and degradation of phosphorylated E-cadherin by activated c-Src.

Indexed as

Epithelial-Mesenchymal TransitionA549 CellsAdenocarcinoma of LungAnimalsAntibodies, MonoclonalAntigens, CDbeta CateninCadherinsCaspase 8Cells, CulturedCSK Tyrosine-Protein KinaseDNA-Binding ProteinsFollow-Up StudiesHumansLung NeoplasmsMaleAntibodies, MonoclonalAntigens, CDbeta CateninCadherinsCaspase 8CDH1 protein, humanCSK protein, humanCSK Tyrosine-Protein KinaseCTNNB1 protein, humanDNA-Binding ProteinsFzd8 protein, humanOncogene ProteinsReceptors, Cell SurfaceRNF43 protein, humanUbiquitin-Protein LigasesVimentinVIM protein, humanCaspase-8C-SrcEMTRNF43

Identifiers

PMID31286874
PMCPMC6613270
OpenAlexW2955144533

What OpenQuestion holds

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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.