Evidence map›Paper›PMID 24096476›Full record

ArticleOncogene2014

Phosphorylation of paxillin confers cisplatin resistance in non-small cell lung cancer via activating ERK-mediated Bcl-2 expression.

D-W Wu, T-C Wu, J-Y Wu, Y-W Cheng, Y-C Chen, M-C Lee, C-Y Chen, H Lee

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

45 citing papers in PubMed, 79 citations in OpenAlex.

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  14. Uncovering the Anti-Lung-Cancer Mechanisms of the Herbal Drug FDY2004 by Network Pharmacology.Evidence-based complementary and alternative medicine : eCAM · 2021
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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

8 authors at 5 institutions in 1 country.

D-W WuGraduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC.
T-C WuDepartment of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
J-Y Wu1] Division of Thoracic Surgery, Buddhist Tzu Chi Taichung General Hospital, Taichung, Taiwan, ROC [2] College of Medicine, Tzu Chi University, Hualien, Taiwan, ROC.
Y-W ChengGraduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC.
Y-C ChenGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taichung, Taiwan, ROC.
M-C LeeDepartment of Thoracic Surgery, Taichung Veteran General Hospital, Taichung, Taiwan, ROC.
C-Y ChenDepartment of Surgery, China Medical University Hospital, Taichung, Taiwan, ROC.
H LeeGraduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan, ROC.
Taipei Medical University · TWBuddhist Tzu Chi General Hospital · TWChina Medical University · TWChung Shan Medical University · TWTaichung Veterans General Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paxillin (PXN) is required for receptor tyrosine kinase-mediated ERK activation, and the activation of the Raf/MEK/ERK cascade has been linked with Bcl-2 expression. We hypothesized that phosphorylation of PXN by the EGFR/Src pathway might contribute to cisplatin resistance via increased Bcl-2 expression. We show that cisplatin resistance was dependent on PXN expression, as evidenced by PXN overexpression in TL-13 and TL-10 cells and PXN knockdown in H23 and CL1-5 cells. Specific inhibitors of signaling pathways indicated that the phosphorylation of PXN at Y118 and Y31 via the Src pathway was responsible for cisplatin resistance. We further demonstrated that ERK activation was also dependent on this PXN phosphorylation. Bcl-2 transcription was upregulated by phosphorylated PXN-mediated ERK activation via increased binding of phosphorylated CREB to the Bcl-2 promoter. A subsequent increase in Bcl-2 levels by a PXN/ERK axis was responsible for the resistance to cisplatin. Animal models further confirmed the findings of in vitro cells indicating that xenograft tumors induced by TL-13-overexpressing cells were successfully suppressed by cisplatin combined with Src or ERK inhibitor compared with treatment of cisplatin, Src inhibitor or ERK inhibitor alone. A positive correlation of phosphorylated PXN with phosphorylated ERK and Bcl-2 was observed in lung tumors from NSCLC patients. Patients with tumors positive for PXN, phosphorylated PXN, phosphorylated ERK and Bcl-2 more commonly showed a poorer response to cisplatin-based chemotherapy than did patients with negative tumors. Collectively, PXN phosphorylation might contribute to cisplatin resistance via activating ERK-mediated Bcl-2 transcription. Therefore, we suggest that Src or ERK inhibitor might be helpful to improve the sensitivity for cisplatin-based chemotherapy in NSCLC patients with PXN-positive tumors.

Indexed as

Drug Resistance, NeoplasmAnimalsAntineoplastic AgentsBenzimidazolesCarcinoma, Non-Small-Cell LungCell Line, TumorCisplatinDasatinibFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMaleMAP Kinase Signaling SystemMiceMice, NudeAntineoplastic AgentsAZD 6244BenzimidazolesCisplatinDasatinibPaxillinPyrimidinesThiazoles

Identifiers

PMID24096476
OpenAlexW2066137841

What OpenQuestion holds

Textmetadata
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.