SPP1 promotes brain metastasis of NSCLC by up-regulating PI3K/AKT/mTOR pathway

Abstract Purpose Brain metastasis (BM) is a significant contributor to poor prognosis in patients with non-small cell lung cancer (NSCLC). Secreted phosphoprotein 1 (SPP1) is involved in the progression and metastasis of various cancers. However, the role of SPP1 in NSCLC, particularly in NSCLC BM, remains unclear. This study aimed to identify genes associated with NSCLC BM and investigate the involvement of SPP1 in NSCLC BM. Methods Integrated genomic analysis was used to identify candidate genes in NSCLC. Expression levels of SPP1 were evaluated in NSCLC tumor tissues and cell lines. In vitro and in vivo experiments were conducted to assess the impact of SPP1 on NSCLC cell behavior and BM. The underlying mechanism involving the PI3K/AKT/mTOR pathway was explored. Results SPP1 expression was found to be elevated in NSCLC tissues and cell lines. SPP1 depletion using shRNA inhibited cell proliferation, migration, and invasion in vitro and suppressed BM in vivo. Mechanistically, SPP1 partly influenced NSCLC progression through the PI3K/AKT/mTOR signaling pathway. Moreover, immunohistochemical staining demonstrated that SPP1 expression was higher in NSCLC tissues with BM than in those without BM. Furthermore, elevated SPP1 expression was associated with poor clinical outcomes in patients with NSCLC. Conclusion This study highlights the role of SPP1 as a regulator of cell metastasis and suggests its potential as a novel therapeutic target for BM in NSCLC.