Evidence map›Paper›PMID 27270426›Full record

ArticleOncogene2017

The ERK-ZEB1 pathway mediates epithelial-mesenchymal transition in pemetrexed resistant lung cancer cells with suppression by vinca alkaloids.

L-Y Chiu, I-L Hsin, T-Y Yang, W-W Sung, J-Y Chi, J T Chang, J-L Ko, G-T Sheu

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
10.5field-weighted citation impact, top 1% 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

64 citing papers in PubMed, 109 citations in OpenAlex.

  1. Article
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  7. Role of microRNA-363 during tumor progression and invasion.Journal of physiology and biochemistry · 2024
    Review
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  11. MAPKs in the early steps of senescence implemEMTation.Frontiers in cell and developmental biology · 2023
    Article
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4 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 1 country.

L-Y ChiuInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
I-L HsinInflammation Research and Drug Development Center, Changhua Christian Hospital, Changhua, Taiwan.
T-Y YangDivision of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
W-W SungSchool of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J-Y ChiInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J T ChangInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J-L KoInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
G-T SheuInstitute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Chung Shan Medical University · TWChanghua Christian Hospital · TWChung Shan Medical University Hospital · TWTaichung Veterans General Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High thymidylate synthase (TS) level in cancer tissue is considered to result in resistance to pemetrexed therapy for advanced stages of nonsquamous non-small cell lung cancers. To further investigate the mechanism of pemetrexed resistance and potential prognostic outcomes in lung cancer, we established pemetrexed-resistant lung adenocarcinoma cell sublines from CL1 harboring a mutated TP53 gene (R248W) and A549 harboring wild-type TP53. We found the TS expression is upregulated in both pemetrexed-resistant sublines and the reduced TS level achieved through shRNA inhibition resulted in higher pemetrexed sensitivity. We also demonstrated that the acquisitions of pemetrexed resistance enhances epithelial-mesenchymal transition (EMT) in vivo with a mice animal model and in vitro with CL1 and A549 sublines, which was associated with upregulation of ZEB1 which, in turn, downregulates E-cadherin and upregulates fibronectin. When ERK1/2 phosphorylation was reduced by an inhibitor (U0126) or siRNA inhibition, both pemetrexed-resistant sublines reduced their migration and invasion abilities. Therefore, the ERK-mediated pathways induce apoptosis with pemetrexed treatment, and may in turn mediate EMT when cancer cells are resistant to pemetrexed. We further demonstrated that the growth of pemetrexed-resistant tumors could be inhibited by vinblastine in vivo and vincristine in vitro. Our data indicate that pemetrexed resistance could be relieved by non-cross-resistant chemotherapeutic drugs such as vinca alkaloids and might be independent to TP53 status. Furthermore, the phosphorylation of ERK was reduced by vincristine. This finding provides a new insight for overcoming pemetrexed resistance and metastasis by application of vinca alkaloids.

Indexed as

A549 CellsAnimalsCell Line, TumorDrug Resistance, NeoplasmEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansLung NeoplasmsMAP Kinase Signaling SystemMicePemetrexedPrognosisTumor Suppressor Protein p53Up-RegulationVinca AlkaloidsXenograft Model Antitumor AssaysPemetrexedTP53 protein, humanTumor Suppressor Protein p53Vinca AlkaloidsZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID27270426
PMCPMC5241427
OpenAlexW2409466177

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.