TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma

Abstract Epithelial–mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal phenotypes. Cancer cells undergo EMT to acquire malignant features and TGF-β is a key regulator of EMT. Here, we demonstrate for the first time that TGF-β could elicit EMT in a mo...

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Autores principales:	Naoya Miyashita, Takayoshi Enokido, Masafumi Horie, Kensuke Fukuda, Hirokazu Urushiyama, Carina Strell, Hans Brunnström, Patrick Micke, Akira Saito, Takahide Nagase
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d422005689cd47d1859b825318bebcb6
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spelling	oai:doaj.org-article:d422005689cd47d1859b825318bebcb62021-11-21T12:23:59ZTGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma10.1038/s41598-021-01799-x2045-2322https://doaj.org/article/d422005689cd47d1859b825318bebcb62021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01799-xhttps://doaj.org/toc/2045-2322Abstract Epithelial–mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal phenotypes. Cancer cells undergo EMT to acquire malignant features and TGF-β is a key regulator of EMT. Here, we demonstrate for the first time that TGF-β could elicit EMT in a mouse lung adenocarcinoma cell line. TGF-β signaling activation led to cell morphological changes corresponding to EMT and enhanced the expression of mesenchymal markers and EMT-associated transcription factors in CMT64 lung cancer cells. RNA-sequencing analyses revealed that TGF-β increases expression of Tead transcription factors and an array of Tead2 target genes. TGF-β stimulation also resulted in alternative splicing of several genes including Cd44, tight junction protein 1 (Tjp1), and Cortactin (Cttn). In parallel with EMT, TGF-β enhanced cell growth of CMT64 cells and promoted tumor formation in a syngeneic transplantation model. Of clinical importance, the expression of TGF-β-induced genes identified in CMT64 cells correlated with EMT gene signatures in human lung adenocarcinoma tissue samples. Furthermore, TGF-β-induced gene enrichment was related to poor prognosis, underscoring the tumor-promoting role of TGF-β signaling in lung adenocarcinoma. Our cellular and syngeneic transplantation model would provide a simple and useful experimental tool to study the significance of TGF-β signaling and EMT.Naoya MiyashitaTakayoshi EnokidoMasafumi HorieKensuke FukudaHirokazu UrushiyamaCarina StrellHans BrunnströmPatrick MickeAkira SaitoTakahide NagaseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naoya Miyashita Takayoshi Enokido Masafumi Horie Kensuke Fukuda Hirokazu Urushiyama Carina Strell Hans Brunnström Patrick Micke Akira Saito Takahide Nagase TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
description	Abstract Epithelial–mesenchymal transition (EMT) is a cellular process during which epithelial cells acquire mesenchymal phenotypes. Cancer cells undergo EMT to acquire malignant features and TGF-β is a key regulator of EMT. Here, we demonstrate for the first time that TGF-β could elicit EMT in a mouse lung adenocarcinoma cell line. TGF-β signaling activation led to cell morphological changes corresponding to EMT and enhanced the expression of mesenchymal markers and EMT-associated transcription factors in CMT64 lung cancer cells. RNA-sequencing analyses revealed that TGF-β increases expression of Tead transcription factors and an array of Tead2 target genes. TGF-β stimulation also resulted in alternative splicing of several genes including Cd44, tight junction protein 1 (Tjp1), and Cortactin (Cttn). In parallel with EMT, TGF-β enhanced cell growth of CMT64 cells and promoted tumor formation in a syngeneic transplantation model. Of clinical importance, the expression of TGF-β-induced genes identified in CMT64 cells correlated with EMT gene signatures in human lung adenocarcinoma tissue samples. Furthermore, TGF-β-induced gene enrichment was related to poor prognosis, underscoring the tumor-promoting role of TGF-β signaling in lung adenocarcinoma. Our cellular and syngeneic transplantation model would provide a simple and useful experimental tool to study the significance of TGF-β signaling and EMT.
format	article
author	Naoya Miyashita Takayoshi Enokido Masafumi Horie Kensuke Fukuda Hirokazu Urushiyama Carina Strell Hans Brunnström Patrick Micke Akira Saito Takahide Nagase
author_facet	Naoya Miyashita Takayoshi Enokido Masafumi Horie Kensuke Fukuda Hirokazu Urushiyama Carina Strell Hans Brunnström Patrick Micke Akira Saito Takahide Nagase
author_sort	Naoya Miyashita
title	TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
title_short	TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
title_full	TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
title_fullStr	TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
title_full_unstemmed	TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
title_sort	tgf-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in cmt64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d422005689cd47d1859b825318bebcb6
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TGF-β-mediated epithelial–mesenchymal transition and tumor-promoting effects in CMT64 cells are reflected in the transcriptomic signature of human lung adenocarcinoma

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