NPM1 Drives ERK1/2-dependent Tumor Progression in Lung Cancer

Abstract Background/Aim: Lung cancer is the most lethal malignancy worldwide, and there remains an urgent need for reliable biomarkers to improve diagnosis and treatment. Nucleophosmin 1 (NPM1), a nucleolar phosphoprotein, has been implicated in hematological cancers, but its significance in lung cancer is less clear. This study investigated the oncogenic role of NPM1 in lung cancer and its involvement in ERK1/2 pathway activation in lung cancer cells. Materials and Methods: Transcriptomic data from TCGA were analyzed to assess NPM1 expression in lung cancer and normal tissues. In vitro assays using A549 and H1299 cells were conducted following siRNA-mediated silencing of NPM1. Cell proliferation, soft agar colony formation, and western blot analyses were performed. In vivo tumorigenicity was tested using a nude mouse xenograft model. Results: NPM1 expression was significantly elevated in lung cancer tissues compared with normal samples. Silencing NPM1 reduced proliferation, colony formation, and tumor growth. Mechanistic studies revealed that NPM1 knockdown decreased phosphorylation of ERK1/2, indicating its role in activating this pathway. Conclusion: NPM1 contributes to lung cancer progression via ERK1/2 signaling. These results highlight NPM1 as a novel oncogene and suggest its potential as a diagnostic and prognostic biomarker in lung cancer.