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Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition

Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition
Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition

Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in which signals transduced by RAS and transforming growth factor (TGF)-β play critical roles. To identify downstream molecular events following RAS and/or TGF-β activation, we performed proteomic analysis using a quantitative label-free approach (LC-HDMS E) to provide in-depth proteome coverage and estimates of protein concentration in absolute amounts. Data are available via ProteomeXchange with identifier PXD023720. We chose ATII ER:KRASV12 as an experimental cell line in which RAS is activated by adding 4-hydroxytamoxifen (4-OHT). Proteomic analysis of ATII cells treated with 4-OHT or TGF-β demonstrated that RAS activation induces an epithelial–mesenchymal transition (EMT) signature. In contrast, under the same conditions, activation of TGF-β signaling alone only induces a partial EMT. EMT is a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties, and is involved in embryonic development, wound healing, fibrosis and cancer metastasis. Thus, these results could help to focus research on the identification of processes that are potentially driving EMT-related human disease.

RAS, TGF-β, epithelial-mesenchymal transition (EMT), fibrosis, lung disease, proteomics
2296-889X
Zhou, Yilu
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Hill, Charlotte
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Yao, Liudi
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Li, Juanjuan
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Hancock, David
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Downward, Julian
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Jones, Mark
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Davies, Donna
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Ewing, Robert
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Skipp, Paul
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Wang, Yihua
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Zhou, Yilu
1878565d-39e6-467d-a027-7320bf4cdaf2
Hill, Charlotte
6d1cfed3-11b1-48af-b171-b8726ab673eb
Yao, Liudi
3c9ce766-5334-49f7-9517-c4dc2013f933
Li, Juanjuan
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Hancock, David
47910329-7a27-4e42-bc5d-ebbd90acbeda
Downward, Julian
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Jones, Mark
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Davies, Donna
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Ewing, Robert
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Skipp, Paul
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Wang, Yihua
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Zhou, Yilu, Hill, Charlotte, Yao, Liudi, Li, Juanjuan, Hancock, David, Downward, Julian, Jones, Mark, Davies, Donna, Ewing, Robert, Skipp, Paul and Wang, Yihua (2021) Quantitative Proteomic Analysis in Alveolar Type II Cells Reveals the Different Capacities of RAS and TGF-β to Induce Epithelial–Mesenchymal Transition. Frontiers in Molecular Biosciences, 8, [595712]. (doi:10.3389/fmolb.2021.595712).

Record type: Article

Abstract

Alveolar type II (ATII) epithelial cells function as stem cells, contributing to alveolar renewal, repair and cancer. Therefore, they are a highly relevant model for studying a number of lung diseases, including acute injury, fibrosis and cancer, in which signals transduced by RAS and transforming growth factor (TGF)-β play critical roles. To identify downstream molecular events following RAS and/or TGF-β activation, we performed proteomic analysis using a quantitative label-free approach (LC-HDMS E) to provide in-depth proteome coverage and estimates of protein concentration in absolute amounts. Data are available via ProteomeXchange with identifier PXD023720. We chose ATII ER:KRASV12 as an experimental cell line in which RAS is activated by adding 4-hydroxytamoxifen (4-OHT). Proteomic analysis of ATII cells treated with 4-OHT or TGF-β demonstrated that RAS activation induces an epithelial–mesenchymal transition (EMT) signature. In contrast, under the same conditions, activation of TGF-β signaling alone only induces a partial EMT. EMT is a dynamic and reversible biological process by which epithelial cells lose their cell polarity and down-regulate cadherin-mediated cell–cell adhesion to gain migratory properties, and is involved in embryonic development, wound healing, fibrosis and cancer metastasis. Thus, these results could help to focus research on the identification of processes that are potentially driving EMT-related human disease.

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Accepted/In Press date: 15 January 2021
Published date: 19 March 2021
Keywords: RAS, TGF-β, epithelial-mesenchymal transition (EMT), fibrosis, lung disease, proteomics

Identifiers

Local EPrints ID: 446511
URI: http://eprints.soton.ac.uk/id/eprint/446511
ISSN: 2296-889X
PURE UUID: a7189291-2ab5-4f29-ac1a-937a685b16b1
ORCID for Juanjuan Li: ORCID iD orcid.org/0000-0003-2164-094X
ORCID for Mark Jones: ORCID iD orcid.org/0000-0001-6308-6014
ORCID for Donna Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Robert Ewing: ORCID iD orcid.org/0000-0001-6510-4001
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

Catalogue record

Date deposited: 12 Feb 2021 17:30
Last modified: 26 Nov 2021 03:12

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Contributors

Author: Yilu Zhou
Author: Charlotte Hill
Author: Liudi Yao
Author: Juanjuan Li ORCID iD
Author: David Hancock
Author: Julian Downward
Author: Mark Jones ORCID iD
Author: Donna Davies ORCID iD
Author: Robert Ewing ORCID iD
Author: Paul Skipp ORCID iD
Author: Yihua Wang ORCID iD

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