Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province 130021, China.
Department of Genetics, College of Basic Medical Sciences, Jilin University, Changchun, Jilin Province 130021, China; Key Laboratory of Neuroimmunology and Clinical Immunology in Jilin Province, Jilin Province 130021, China.
Int Immunopharmacol. 2024 Dec 5;142(Pt B):113170. doi: 10.1016/j.intimp.2024.113170. Epub 2024 Sep 16.
Activin A, a member of the transforming growth factor β (TGF-β) superfamily, is involved in tumorigenesis and tumor progression. However, it remains unclear whether activin A can affect the migration of lung adenocarcinoma (LUAD) cells. In this study, the results of differentially expressed genes (DEGs) identification revealed that lung adenocarcinoma tissues exhibited lower expression of activin βA mRNA, but higher expression of epidermal growth factor (EGF) and MMP9 mRNA compared to nontumor tissues. Moreover, we found that activin A inhibited human LUAD A549 cell proliferation promoted by EGF. Additionally, EGF induced A549 cell migration in microfluidic device, while activin A attenuated EGF actions. Simultaneously, EGF increased the levels of migration-related proteins, but activin A played the opposite role. Furthermore, the study revealed that EGF upregulated the ratio of p-ERK/ERK in A549 cells, which was weakened by activin A, and A549 cell migration regulated by activin A was not related to calcium signaling. In addition, the inhibitory effect of activin A on EGF-induced A549 cell migration was attenuated by the ERK inhibitor FR180204. These findings demonstrate that activin A effectively hinders the migration of A549 cells induced by EGF through ERK1/2 signaling, suggesting that targeting activin A may hold promise in the treatment of EGF-dependent LUAD growth and metastasis.
激活素 A 是转化生长因子 β（TGF-β）超家族的成员，参与肿瘤发生和肿瘤进展。然而，目前尚不清楚激活素 A 是否能影响肺腺癌（LUAD）细胞的迁移。在这项研究中，差异表达基因（DEGs）鉴定的结果表明，与非肿瘤组织相比，肺腺癌组织中激活素 βA mRNA 的表达较低，而表皮生长因子（EGF）和 MMP9 mRNA 的表达较高。此外，我们发现激活素 A 抑制了 EGF 促进的人 LUAD A549 细胞增殖。此外，EGF 在微流控装置中诱导 A549 细胞迁移，而激活素 A 则减弱了 EGF 的作用。同时，EGF 增加了迁移相关蛋白的水平，但激活素 A 则起到相反的作用。此外，研究表明 EGF 上调了 A549 细胞中 p-ERK/ERK 的比值，而激活素 A 则削弱了这一比值，激活素 A 调节的 A549 细胞迁移与钙信号无关。此外，ERK 抑制剂 FR180204 减弱了激活素 A 对 EGF 诱导的 A549 细胞迁移的抑制作用。这些发现表明，激活素 A 通过 ERK1/2 信号有效抑制了 EGF 诱导的 A549 细胞迁移，提示靶向激活素 A 可能有望用于治疗 EGF 依赖性 LUAD 生长和转移。
