Abstract
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.
Highlights
Lung cancer is one of the most genetically complex, aggressive, and lethal solid malignancies [1]
Accumulating evidence showed that Epithelial membrane proteins (EMPs) exhibit both prometastatic and antimetastatic functions, which are likely involved in the complex mechanisms of cancer progression [20]
We analyzed the expression of EMPs and explored the biological function of epithelial membrane protein 2 (EMP2) as well as exosomes derived from EMP2-overexpressing cells in non-small cell lung cancer (NSCLC) development
Summary
Lung cancer is one of the most genetically complex, aggressive, and lethal solid malignancies [1]. NSCLCs can be further subclassified into several groups, containing squamous cell carcinoma (SCC), adenocarcinoma (ADC), and large cell carcinoma (LCLC) [3]. Over the past two decades, progress has been made in management of lung cancer due to early diagnosis through screening with low-dose computed tomography and implementation of biomarker-driven therapy, including targeted therapy and immunotherapy; the five-year survival rate is still lower than 21% [4]. As lung cancer is a heterogeneous disease, multiple predictive and prognostic biomarkers need to be identified to ensure better patient response to treatment. Characterization of novel biomarkers could help to further understand the molecular biology of the disease, improve early diagnosis, and develop new personalized therapies, which may eventually contribute to better clinical outcomes
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