Evidence map›Paper›PMID 27167206›Full record

ArticleOncotarget2016

JWA loss promotes cell migration and cytoskeletal rearrangement by affecting HER2 expression and identifies a high-risk subgroup of HER2-positive gastric carcinoma patients.

Jing Qian, Weiyou Zhu, Keming Wang, Lin Ma, Jin Xu, Tongpeng Xu, Oluf Dimitri Røe, Aiping Li, Jianwei Zhou, Yongqian Shu

Open access · diamondAbstract read
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.6field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

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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

10 authors at 4 institutions in 3 countries.

Jing QianDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Weiyou ZhuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Keming WangDepartment of Oncology, The Secondary Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Lin MaDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jin XuDepartment of Molecular Cell Biology and Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention & Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Tongpeng XuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Oluf Dimitri RøeDepartment of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Aiping LiDepartment of Molecular Cell Biology and Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention & Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Jianwei ZhouDepartment of Molecular Cell Biology and Toxicology, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention & Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Yongqian ShuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Nanjing Medical University · CNAalborg University Hospital · DKJiangsu Province Hospital · CNSecond Affiliated Hospital of Nanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsJWA, a microtubule-associated protein (MAP) involved in apoptosis, has been identified as a suppressor of metastasis, and it affects cell migration in melanoma and its downregulation in tumor is an idependent negative prognostic factor in resectable gastric cancer. HER2 overexpression has been observed in gastric cancer (GC) cells and implicated in the metastatic phenotype. However, the biological role of JWA in migration and its clinical value in HER2-positive GC remain elusive.

resultsJWA suppresses EGF-induced cell migration and actin cytoskeletal rearrangement by abrogating HER2 expression and downstream PI3K/AKT signaling in HER2-overexpressing GC cell lines. The modulation of HER2 by JWA is dependent on ERK activation and consequent PEA3 upregulation and activation. Reduced JWA expression is associated with high HER2 expression and with poor survival in patients with AGC, whereas HER2 expression alone is not associated with survival. However, concomitant low JWA and high HER2 expression is associated with unfavorable outcomes. Additionally, when patients were stratified by JWA expression, those with higher HER2 expression in the low JWA expression subgroup exhibited worse survival.

methodsThe impact of JWA on the EGF-induced migration of HER2-positive GC cells was studied using transwell assays and G-LISA assays. Western blotting, real-time PCR, electrophoretic mobility shift assays and luciferase assays were utilized to investigate the mechanisms by which JWA affects HER2. The association of JWA with HER2 and its clinical value were further analyzed by IHC in 128 pairs of advanced gastric cancer (AGC) and adjacent normal tissue samples.

conclusionsThis study characterizes a novel mechanism for regulating cell motility in HER2-overexpressing GC cells involving JWA-mediated MEK/ERK/PEA3 signaling activation and HER2 downregulation. Furthermore, JWA may be a useful prognostic indicator for advanced GC and may help stratify HER2-positive patient subgroups to better identify unfavorable outcomes.

Indexed as

AdultAgedBiomarkers, TumorCell MovementCytoskeletonErb-b2 Receptor Tyrosine KinasesFemaleGene Expression Regulation, NeoplasticHeat-Shock ProteinsHumansIntracellular Signaling Peptides and ProteinsKaplan-Meier EstimateMaleMembrane Transport ProteinsMiddle AgedPrognosisARL6IP5 protein, humanBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHeat-Shock ProteinsIntracellular Signaling Peptides and ProteinsMembrane Transport Proteinscell migrationgastric cancerHER2JWAPEA3

Identifiers

PMID27167206
PMCPMC5095045
OpenAlexW2346035167

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.