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Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation

Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenc...

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Autores principales: Wang, Aman, Lu, Chang, Ning, Zhen, Gao, Wei, Xie, Yunpeng, Zhang, Ningning, Liang, Jinxiao, Abbasi, Faisal S., Yan, Qiu, Liu, Jiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438647/
https://www.ncbi.nlm.nih.gov/pubmed/28423676
http://dx.doi.org/10.18632/oncotarget.16001
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author Wang, Aman
Lu, Chang
Ning, Zhen
Gao, Wei
Xie, Yunpeng
Zhang, Ningning
Liang, Jinxiao
Abbasi, Faisal S.
Yan, Qiu
Liu, Jiwei
author_facet Wang, Aman
Lu, Chang
Ning, Zhen
Gao, Wei
Xie, Yunpeng
Zhang, Ningning
Liang, Jinxiao
Abbasi, Faisal S.
Yan, Qiu
Liu, Jiwei
author_sort Wang, Aman
collection PubMed
description Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-β1(TGF-β1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY- mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma.
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spelling pubmed-54386472017-05-24 Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation Wang, Aman Lu, Chang Ning, Zhen Gao, Wei Xie, Yunpeng Zhang, Ningning Liang, Jinxiao Abbasi, Faisal S. Yan, Qiu Liu, Jiwei Oncotarget Research Paper Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis. Here, we found that in lung adenocarcinoma samples, the density of TAMs correlates with E-cadherin level and LeY level. In vitro assays, M2 macrophages promoted FUT4/LeY expression through the transforming growth factor-β1(TGF-β1)/Smad2/3 signaling pathway. FUT4/LeY was indispensable in M2 macrophages-mediated cytoskeletal remodeling and EMT. Furthermore, fucosylation of Ezrin mediated by FUT4/LeY can promote the phosphorylation of Ezrin, which was the critical mechanism of M2 macrophages-induced EMT. In vivo assays confirmed that M2 macrophages promoted EMT through the up-regulation of LeY and phosphorylated Ezrin. Together, our results revealed that TAMs promote Ezrin phosphorylation-mediated EMT in lung adenocarcinoma through FUT4/LeY- mediated fucosylation. Targeting this newly identified signaling may offer new possibilities for immunotherapy in lung adenocarcinoma. Impact Journals LLC 2017-03-08 /pmc/articles/PMC5438647/ /pubmed/28423676 http://dx.doi.org/10.18632/oncotarget.16001 Text en Copyright: © 2017 Wang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Aman
Lu, Chang
Ning, Zhen
Gao, Wei
Xie, Yunpeng
Zhang, Ningning
Liang, Jinxiao
Abbasi, Faisal S.
Yan, Qiu
Liu, Jiwei
Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title_full Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title_fullStr Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title_full_unstemmed Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title_short Tumor-associated macrophages promote Ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through FUT4/LeY up-regulation
title_sort tumor-associated macrophages promote ezrin phosphorylation-mediated epithelial-mesenchymal transition in lung adenocarcinoma through fut4/ley up-regulation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438647/
https://www.ncbi.nlm.nih.gov/pubmed/28423676
http://dx.doi.org/10.18632/oncotarget.16001
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