Cargando…
Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway
Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biolo...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999101/ https://www.ncbi.nlm.nih.gov/pubmed/33799364 http://dx.doi.org/10.3390/ijms22062944 |
_version_ | 1783670705547640832 |
---|---|
author | Ma, Yunxia Schröder, Desiree Charlotte Nenkov, Miljana Rizwan, Maryam Noor Abubrig, Mohamed Sonnemann, Jürgen Murrieta-Coxca, José M. Morales-Prieto, Diana M. Westermann, Martin Gaßler, Nikolaus Chen, Yuan |
author_facet | Ma, Yunxia Schröder, Desiree Charlotte Nenkov, Miljana Rizwan, Maryam Noor Abubrig, Mohamed Sonnemann, Jürgen Murrieta-Coxca, José M. Morales-Prieto, Diana M. Westermann, Martin Gaßler, Nikolaus Chen, Yuan |
author_sort | Ma, Yunxia |
collection | PubMed |
description | Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs. |
format | Online Article Text |
id | pubmed-7999101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79991012021-03-28 Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway Ma, Yunxia Schröder, Desiree Charlotte Nenkov, Miljana Rizwan, Maryam Noor Abubrig, Mohamed Sonnemann, Jürgen Murrieta-Coxca, José M. Morales-Prieto, Diana M. Westermann, Martin Gaßler, Nikolaus Chen, Yuan Int J Mol Sci Article Epithelial membrane proteins (EMP1-3) are involved in epithelial differentiation and carcinogenesis. Dysregulated expression of EMP2 was observed in various cancers, but its role in human lung cancer is not yet clarified. In this study, we analyzed the expression of EMP1-3 and investigated the biological function of EMP2 in non-small cell lung cancer (NSCLC). The results showed that lower expression of EMP1 was significantly correlated with tumor size in primary lung tumors (p = 0.004). Overexpression of EMP2 suppressed tumor cell growth, migration, and invasion, resulting in a G1 cell cycle arrest, with knockdown of EMP2 leading to enhanced cell migration, related to MAPK pathway alterations and disruption of cell cycle regulatory genes. Exosomes isolated from transfected cells were taken up by tumor cells, carrying EMP2-downregulated microRNAs (miRNAs) which participated in regulation of the tumor microenvironment. Our data suggest that decreased EMP1 expression is significantly related to increased tumor size in NSCLC. EMP2 suppresses NSCLC cell growth mainly by inhibiting the MAPK pathway. EMP2 might further affect the tumor microenvironment by regulating tumor microenvironment-associated miRNAs. MDPI 2021-03-14 /pmc/articles/PMC7999101/ /pubmed/33799364 http://dx.doi.org/10.3390/ijms22062944 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ma, Yunxia Schröder, Desiree Charlotte Nenkov, Miljana Rizwan, Maryam Noor Abubrig, Mohamed Sonnemann, Jürgen Murrieta-Coxca, José M. Morales-Prieto, Diana M. Westermann, Martin Gaßler, Nikolaus Chen, Yuan Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title | Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title_full | Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title_fullStr | Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title_full_unstemmed | Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title_short | Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway |
title_sort | epithelial membrane protein 2 suppresses non-small cell lung cancer cell growth by inhibition of mapk pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999101/ https://www.ncbi.nlm.nih.gov/pubmed/33799364 http://dx.doi.org/10.3390/ijms22062944 |
work_keys_str_mv | AT mayunxia epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT schroderdesireecharlotte epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT nenkovmiljana epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT rizwanmaryamnoor epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT abubrigmohamed epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT sonnemannjurgen epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT murrietacoxcajosem epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT moralesprietodianam epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT westermannmartin epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT gaßlernikolaus epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway AT chenyuan epithelialmembraneprotein2suppressesnonsmallcelllungcancercellgrowthbyinhibitionofmapkpathway |