Epithelial Membrane Protein 2 Suppresses Non-Small Cell Lung Cancer Cell Growth by Inhibition of MAPK Pathway
| Autor: | Yunxia Ma, Desiree Charlotte Schröder, Miljana Nenkov, Maryam Noor Rizwan, Mohamed Abubrig, Jürgen Sonnemann, José M. Murrieta-Coxca, Diana M. Morales-Prieto, Martin Westermann, Nikolaus Gaßler, Yuan Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
tumor pathways Receptors Cell Surface NSCLC Exosomes Article lcsh:Chemistry Cell Movement Carcinoma Non-Small-Cell Lung Cell Line Tumor Tumor Microenvironment exosome Humans lcsh:QH301-705.5 Aged Cell Proliferation Mitogen-Activated Protein Kinase Kinases Membrane Glycoproteins microRNA Cell Cycle Checkpoints Middle Aged Neoplasm Proteins Gene Expression Regulation Neoplastic MicroRNAs lcsh:Biology (General) lcsh:QD1-999 Female epithelial membrane protein Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 6 International Journal of Molecular Sciences, Vol 22, Iss 2944, p 2944 (2021) |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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