Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Cancer Med. 2023 Jan;12(2):1630-1642. doi: 10.1002/cam4.4987. Epub 2022 Jun 30.
As a member of the Ephrin protein family that elicits short distance cell-cell signaling, EphrinA3 has been shown to promote or inhibit tumorigenesis depending on tumor types, but its roles and the underlying mechanisms in lung adenocarcinoma (LUAD) have not been reported.
The TCGA database and Kaplan-Meier Plotter database were used to analyze the differential expression of EphrinA3 between LUAD and para-carcinoma tissues, and its effect on overall survival of LUAD patients. CCK-8 assay, Edu assay, and flow cytometry were used to probe the effect of EphrinA3 on the proliferation of LUAD cells, and transwell assay was employed to examine its effect on migration and invasion. In addition, the effect of EphrinA3 on the growth of LUAD was further evaluated using a xenograft tumor model.
EphrinA3 was expressed highly in LUAD, and its expression level was negatively correlated with the prognosis of LUAD patients. In addition, EphrinA3 promoted proliferation, migration, and invasion of LUAD cells, and accelerated tumor growth in a xenograft LUAD model. The reported EphrinA3 receptors, EphA1 and EphA10, were expressed in clinical LUAD tissues and co-localized with EphrinA3 in LUAD cells. Mechanistically, EphrinA3/Eph signaling activated AKT, ERK, and p38MAPK, induced epithelial-mesenchymal transition (EMT), and upregulated matrix metalloproteases-2 and -9 (MMP-2/-9).
EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.
作为 Ephrin 蛋白家族的一员，EphrinA3 通过短程细胞-细胞信号传递发挥作用，其在不同肿瘤类型中促进或抑制肿瘤发生的作用尚不一致，但 EphrinA3 在肺腺癌（LUAD）中的作用及其潜在机制尚未见报道。
TCGA 数据库和 Kaplan-Meier Plotter 数据库用于分析 LUAD 和癌旁组织中 EphrinA3 的差异表达及其对 LUAD 患者总生存期的影响。CCK-8 检测、Edu 检测和流式细胞术用于探讨 EphrinA3 对 LUAD 细胞增殖的影响，Transwell 检测用于检测其对迁移和侵袭的影响。此外，还使用异种移植 LUAD 模型进一步评估 EphrinA3 对 LUAD 生长的影响。
EphrinA3 在 LUAD 中高表达，其表达水平与 LUAD 患者的预后呈负相关。此外，EphrinA3 促进 LUAD 细胞的增殖、迁移和侵袭，并加速异种移植 LUAD 模型中的肿瘤生长。报道的 EphrinA3 受体 EphA1 和 EphA10 在临床 LUAD 组织中表达，并与 LUAD 细胞中的 EphrinA3 共定位。在机制上，EphrinA3/Eph 信号激活 AKT、ERK 和 p38MAPK，诱导上皮-间充质转化（EMT），并上调基质金属蛋白酶-2 和 -9（MMP-2/-9）。
EphrinA3 的表达与 LUAD 患者的预后呈负相关。EphrinA3 促进 LUAD 细胞的增殖、迁移和侵袭。EphrinA3 增强 ERK 和 AKT 的磷酸化，增强 LUAD 细胞中的 EMT 和 MMP 表达。
