Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.
Department of Pediatric Hematology and Oncology, Children's Clinic, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.
Int J Mol Sci. 2021 Mar 14;22(6):2944. doi: 10.3390/ijms22062944.
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 ( = 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.
上皮膜蛋白（EMP1-3）参与上皮细胞分化和癌变。在各种癌症中观察到 EMP2 的表达失调，但它在人类肺癌中的作用尚不清楚。在这项研究中，我们分析了 EMP1-3 的表达，并研究了 EMP2 在非小细胞肺癌（NSCLC）中的生物学功能。结果表明，原发性肺肿瘤中 EMP1 的低表达与肿瘤大小显著相关（=0.004）。EMP2 的过表达抑制肿瘤细胞的生长、迁移和侵袭，导致 G1 细胞周期停滞，而 EMP2 的敲低导致细胞迁移增强，与 MAPK 途径改变和细胞周期调节基因的破坏有关。转染细胞分离的外泌体被肿瘤细胞摄取，携带 EMP2 下调的 microRNAs（miRNAs），参与肿瘤微环境的调节。我们的数据表明，NSCLC 中 EMP1 表达的降低与肿瘤大小的增加显著相关。EMP2 主要通过抑制 MAPK 途径抑制 NSCLC 细胞的生长。EMP2 可能通过调节与肿瘤微环境相关的 miRNAs 进一步影响肿瘤微环境。
