MAGEA1 drives tumor progression via activation of the AKT pathway and correlates with elevated radiosensitivity in lung adenocarcinoma.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Identifying novel molecular mechanisms underlying its progression and treatment resistance is crucial. MAGEA1, a cancer-testis antigen, exhibits oncogenic functions in multiple solid tumors; however, its expression profile and precise role in NSCLC remain poorly defined. MAGEA1 expression in NSCLC versus normal tissue was analyzed via TCGA bioinformatics, and differential expression was orthogonally validated by RT-qPCR and Western blot in normal lung epithelial and lung adenocarcinoma cell lines. Cellular proliferation, migration, and invasion were assessed by CCK-8 and Transwell assays. Apoptosis and radiosensitivity were evaluated using flow cytometry, colony formation, immunofluorescence, and comet assays. In vivo tumor growth and metastasis was examined in subcutaneous and lung metastasis mouse models. Downstream pathways were explored via RNA-seq. MAGEA1 was significantly upregulated in NSCLC tissues. Its overexpression promoted lung adenocarcinoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and in vivo tumor growth and metastasis, whereas MAGEA1 knockdown reversed these effects. Moreover, MAGEA1 overexpression increased irradiation-induced DNA damage and apoptosis and decreased clonogenic survival, indicating increased radiosensitivity. Mechanistically, MAGEA1 exerted its oncogenic effects primarily through activation of the AKT pathway. This study demonstrates that MAGEA1 drives lung adenocarcinoma progression by activating the PI3K/AKT pathway and correlates with elevated radiosensitivity, highlighting its potential as a therapeutic target in lung adenocarcinoma.