Evidence map›Paper›PMID 29986466›Full record

ArticleInternational journal of molecular sciences2018

Label-Free Quantitative Proteomics Combined with Biological Validation Reveals Activation of Wnt/β-Catenin Pathway Contributing to Trastuzumab Resistance in Gastric Cancer.

Wenhu Liu, Jiangbei Yuan, Zhenzhong Liu, Jianwu Zhang, Jinxia Chang

Open access · goldAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.3field-weighted citation impact, top 16% 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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  10. Mechanisms of resistance to trastuzumab in HER2-positive gastric cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    Article
  11. Review
  12. Article
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  14. Cancers · 2022
    Article
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  16. Review
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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

5 authors at 2 institutions in 1 country.

Wenhu LiuDepartment of Medicinal Chemistry, Department of Pharmacology, School of Pharmacy, North Sichuan Medical College, Nanchong 637100, China. wenhuliu@cqu.edu.cn.ORCID 0000-0002-6545-157X
Jiangbei YuanSchool of Pharmaceutical Sciences and Innovative Drug Research Center, Chongqing University, Chongqing 401331, China. yuanjiangbei@cqu.edu.cn.
Zhenzhong LiuDepartment of Preventive Medicine, North Sichuan Medical College, Nanchong 637100, China. liuzhenzhong@nsmc.edu.cn.
Jianwu ZhangDepartment of Medicinal Chemistry, Department of Pharmacology, School of Pharmacy, North Sichuan Medical College, Nanchong 637100, China. jianwuzhang@nsmc.edu.cn.
Jinxia ChangInnovative Platform of Basic Medical Sciences, Department of Microbiology and Immunology, School of Basic Medical Sciences, North Sichuan Medical College, Nanchong 637100, China. jinxiachang@nsmc.edu.cn.
North Sichuan Medical University · CNChongqing University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to trastuzumab, which specifically target HER2-positive breast and gastric cancer, can develop ultimately in cancer patients. However, the underlying mechanisms of resistance in gastric cancer have not been fully elucidated. Here, we established trastuzumab-resistant MKN45 and NCI N87 gastric cancer sublines from their parental cells. The resistant cells exhibited characteristics of epithelial-mesenchymal transition (EMT) and acquired higher migratory and invasive capacities. To exploit the activated pathways and develop new strategies to overcome trastuzumab resistance, we investigated MKN45 and MKN45/R cells via label-free quantitative proteomics, and found pathways that were altered significantly in MKN45/R cells, with the Wnt/β-catenin pathway being the most significant. We further confirmed the activation of this pathway by detecting its key molecules in MKN45/R and NCI N87/R cells via Western blot, in which Wnt3A, FZD6, and CTNNB1 increased, whereas GSK-3β decreased, manifesting the activation of the Wnt/&-catenin pathway. Correspondingly, inhibition of Wnt/β-catenin pathway by ICG-001, a specific Wnt/&-catenin inhibitor, preferentially reduced proliferation and invasion of trastuzumab-resistant cells and reversed EMT. Concurringly, CTNNB1 knockdown in stable cell lines potently sensitized cells to trastuzumab and induced more apoptosis. Taken together, our study demonstrates that the Wnt/β-catenin pathway mediates trastuzumab resistance, and the combination of Wnt/β-catenin inhibitors with trastuzumab may be an effective treatment option.

Indexed as

Drug Resistance, NeoplasmProteomicsAntineoplastic Agents, ImmunologicalApoptosisBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHumansNeoplasm InvasivenessPyrimidinonesStomach NeoplasmsTrastuzumabWnt Signaling PathwayAntineoplastic Agents, ImmunologicalBridged Bicyclo Compounds, HeterocyclicICG 001PyrimidinonesTrastuzumabEMTgastric cancerlabel-free quantitative proteomicstrastuzumab resistanceWnt/β-catenin pathway

Identifiers

PMID29986466
PMCPMC6073113
OpenAlexW2845000172

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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.