Evidence map›Paper›PMID 28423617›Full record

ArticleOncotarget2017

The E3 ubiquitin ligase NEDD4 is translationally upregulated and facilitates pancreatic cancer.

Min Weng, Zhu-Lin Luo, Xiao-Ling Wu, Wei-Zheng Zeng

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

11 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022
    Review
  7. Review
  8. Article
  9. Article
  10. Reduced PDZRN4 promotes breast cancer progression and predicts poor prognosis.International journal of clinical and experimental pathology · 2019
    Article
  11. Article
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

4 authors at 1 institution in 1 country.

Min WengDepartment of Gastroenterology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
Zhu-Lin LuoDepartment of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
Xiao-Ling WuDepartment of Gastroenterology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
Wei-Zheng ZengDepartment of Gastroenterology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, China.
Chengdu Military General Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimTo determine the regulation and function of the neural precursor cell expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT signaling.

methodsWe investigated the expression of NEDD4 and the tumor suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and migration. We subsequently determined the crosstalk between NEDD4 expression and the PTEN/PI3K/AKT signaling pathway. Finally, we determined the mechanism behind differential NEDD4 protein expression in pancreatic cancer.

resultsThe expression of NEDD4 was heterogeneous in PDAC cells, but was significantly higher compared to normal pancreatic ductal epithelial cells. Analogically, PTEN was decreased in the PDAC cells. A combination of MTT assay, wound healing migration assay, and transwell invasion assays confirmed that depletion of NEDD4 decreased the proliferation and migration ability of PDAC cells. Western blot and immunofluorescence results revealed that NEDD4 could affect PTEN/PI3K/AKT signaling pathway in PDAC cells. Polysomal profiling revealed that higher NEDD4 protein expression in PDAC cells was due to undefined mechanism involving translational activation.

conclusionsOur results reveal a novel mechanism of upregulation of NEDD4 expression in PDAC. Our findings indicate that NEDD4 potentially plays a critical role in activating the PI3K/AKT signaling pathway by negatively regulating PTEN levels in PDAC cells, which promotes pancreatic cancer cell proliferation and metastasis. Therefore, NEDD4 may be a potential therapeutic target in PDAC.

Indexed as

AdenocarcinomaBlotting, WesternEndosomal Sorting Complexes Required for TransportFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansNedd4 Ubiquitin Protein LigasesPancreatic NeoplasmsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseReal-Time Polymerase Chain ReactionTranscriptional ActivationTranscriptomeUbiquitin-Protein LigasesUp-RegulationAKT1 protein, humanEndosomal Sorting Complexes Required for TransportNedd4 protein, humanNedd4 Ubiquitin Protein LigasesProto-Oncogene Proteins c-aktPTEN PhosphohydrolasePTEN protein, humanUbiquitin-Protein LigasesNEDD4pancreatic ductal adenocarcinomaPDACPI3K/AKTPTEN

Identifiers

PMID28423617
PMCPMC5386762
OpenAlexW2589309991

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.