Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer

Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of...

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Autores principales:	Yunxia Ma, Miljana Nenkov, Desiree Charlotte Schröder, Mohamed Abubrig, Nikolaus Gassler, Yuan Chen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	NSCLC FBLN2 DNA methylation cell adhesion ECM Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/f809da4250124a7d8fb38776e51fea89
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spelling	oai:doaj.org-article:f809da4250124a7d8fb38776e51fea892021-11-11T17:16:00ZFibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer10.3390/ijms2221118341422-00671661-6596https://doaj.org/article/f809da4250124a7d8fb38776e51fea892021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11834https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of FBLN2 in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we found that FBLN2 was downregulated in 9 out of 11 lung cancer cell lines compared to normal bronchial epithelial cells, which was associated with DNA hypermethylation. Primary lung squamous cell carcinoma expressed significantly more FBLN2 protein compared to adenocarcinoma (<i>p</i> = 0.047). Ectopic expression of FBLN2 led to decreased cell proliferation, migration and invasion, accompanied by inactivated MAPK/ERK and AKT/mTOR pathways, while FBLN2 siRNA knockdown resulted in an opposite biological behaviour in NSCLC cells. Additionally, overexpression of FBLN2 led to dysregulation of cell adhesion molecules, ECM markers and a panel of lysate/exosome-derived-microRNAs, which are involved in cell adhesion and ECM remodelling. Taken together, our data indicate that FBLN2 is methylated and exerts a tumor suppressor function through modulation of MAPK/ERK and AKT pathways and regulation of cell adhesion and ECM genes. Moreover, FBLN2 might be a potential biomarker for the sub-classification of NSCLC.Yunxia MaMiljana NenkovDesiree Charlotte SchröderMohamed AbubrigNikolaus GasslerYuan ChenMDPI AGarticleNSCLCFBLN2DNA methylationcell adhesionECMBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11834, p 11834 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	NSCLC FBLN2 DNA methylation cell adhesion ECM Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	NSCLC FBLN2 DNA methylation cell adhesion ECM Biology (General) QH301-705.5 Chemistry QD1-999 Yunxia Ma Miljana Nenkov Desiree Charlotte Schröder Mohamed Abubrig Nikolaus Gassler Yuan Chen Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
description	Fibulins (FBLNs), interacting with cell adhesion receptors and extracellular matrix (ECM) components, play multiple roles in ECM structures and tissue functions. Abnormal expression of FBLN2, one of the fibulin family members, contributes to tumor initiation and development. However, the function of FBLN2 in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In this study, we found that FBLN2 was downregulated in 9 out of 11 lung cancer cell lines compared to normal bronchial epithelial cells, which was associated with DNA hypermethylation. Primary lung squamous cell carcinoma expressed significantly more FBLN2 protein compared to adenocarcinoma (<i>p</i> = 0.047). Ectopic expression of FBLN2 led to decreased cell proliferation, migration and invasion, accompanied by inactivated MAPK/ERK and AKT/mTOR pathways, while FBLN2 siRNA knockdown resulted in an opposite biological behaviour in NSCLC cells. Additionally, overexpression of FBLN2 led to dysregulation of cell adhesion molecules, ECM markers and a panel of lysate/exosome-derived-microRNAs, which are involved in cell adhesion and ECM remodelling. Taken together, our data indicate that FBLN2 is methylated and exerts a tumor suppressor function through modulation of MAPK/ERK and AKT pathways and regulation of cell adhesion and ECM genes. Moreover, FBLN2 might be a potential biomarker for the sub-classification of NSCLC.
format	article
author	Yunxia Ma Miljana Nenkov Desiree Charlotte Schröder Mohamed Abubrig Nikolaus Gassler Yuan Chen
author_facet	Yunxia Ma Miljana Nenkov Desiree Charlotte Schröder Mohamed Abubrig Nikolaus Gassler Yuan Chen
author_sort	Yunxia Ma
title	Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
title_short	Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
title_full	Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
title_fullStr	Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
title_full_unstemmed	Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer
title_sort	fibulin 2 is hypermethylated and suppresses tumor cell proliferation through inhibition of cell adhesion and extracellular matrix genes in non-small cell lung cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f809da4250124a7d8fb38776e51fea89
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Fibulin 2 Is Hypermethylated and Suppresses Tumor Cell Proliferation through Inhibition of Cell Adhesion and Extracellular Matrix Genes in Non-Small Cell Lung Cancer

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