Evidence map›Paper›PMID 24113182›Full record

ArticleCell death & disease2013

Loss of TAK1 increases cell traction force in a ROS-dependent manner to drive epithelial-mesenchymal transition of cancer cells.

C R I Lam, C Tan, Z Teo, C Y Tay, T Phua, Y L Wu, P Q Cai, L P Tan, X Chen, P Zhu and 1 more

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

Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.4field-weighted citation impact, top 13% 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

28 citing papers in PubMed, 49 citations in OpenAlex.

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  8. Cross-Talk between Oxidative Stress and mOxidative medicine and cellular longevity · 2021
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  11. In Vivo Imaging with Genetically Encoded Redox Biosensors.International journal of molecular sciences · 2020
    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

11 authors at 1 institution in 3 countries.

C R I LamSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore.
C Tan
Z Teo
C Y Tay
T Phua
Y L Wu
P Q Cai
L P Tan
X Chen
P Zhu
N S Tan
Nanyang Technological University · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ-SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFβ-TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5β1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFβ1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFβ-TAK1 and TGFβ-SMAD pathways is pivotal for TGFβ1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.

Indexed as

AnimalsBiomechanical PhenomenaCell Line, TumorCell MembraneEpithelial-Mesenchymal TransitionHEK293 CellsHumansIntegrin beta1Integrin beta3MAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceModels, BiologicalNeoplasm InvasivenessNeoplasms, Squamous CellOxidation-ReductionIntegrin beta1Integrin beta3MAP Kinase Kinase Kinase 7MAP Kinase Kinase Kinasesrac1 GTP-Binding ProteinReactive Oxygen Speciesrho GTP-Binding ProteinsSmad ProteinsTransforming Growth Factor beta1

Identifiers

PMID24113182
PMCPMC3824649
OpenAlexW1993368552

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.