Nucleophosmin promotes lung adenocarcinoma cell proliferation, migration and invasion by activating the EGFR/MAPK signaling pathway.

Abstract

Lung adenocarcinoma (LUAD) is the main cause of death globally. The present study investigated the prognostic value and functional verification of nucleophosmin (NPM1) in LUAD. LUAD and normal samples from The Cancer Genome Atlas were analyzed to identify whether NPM1 is associated with LUAD prognosis. NPM1 protein expression level was verified by western blotting. Cell proliferation, migration and invasion were detected by Cell Counting Kit‑8, wound healing and Transwell assays, respectively. EGFR/MAPK pathway‑related proteins [phosphorylated (p)‑EGFR/EGFR, p‑MEK/MEK, and p‑ERK/ERK] expression was measured through western blotting. A xenograft tumor mice model was constructed to perform the in vivo verification. NPM1 was upregulated in LUAD cells, and high‑level NPM1 indicated poor prognosis in patients with LUAD. In vitro experiments revealed that NPM1 knockdown inhibited LUAD cell proliferation, migration and invasion. Moreover, protein expression of p‑EGFR/EGFR, p‑MEK/MEK and p‑ERK/ERK was reduced with the NPM1 silencing. Furthermore, EGF, an activator of the EGFR/MAPK pathway, reversed the effects of NPM1. In vivo experiments showed that NPM1 knockdown inhibited tumor growth and protein levels of p‑EGFR/EGFR, p‑MEK/MEK and p‑ERK/ERK. NPM1 is related to the poor prognosis of LUAD and promotes the malignant progression of LUAD by activating the EGFR/MAPK pathway. This discovery provides a new potential therapeutic target for the diagnosis and treatment of LUAD.