IGFBP1 facilitates tumor proliferation, invasion and migration by modulating the MAPK-ERK signaling pathway in lung adenocarcinoma.

[OBJECTIVE] Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, and lymph node metastasis serves as a significant prognostic risk factor. The identification of molecular biomarkers associated with lymph node metastasis holds paramount importance in the prevention and treatment strategies for this condition.

[METHODS] Through bioinformatic analysis, we identified insulin-like growth factor binding protein 1 (IGFBP1) as the biomarker most strongly associated with lymph node metastasis. Subsequently, we performed proliferation, invasion, and migration assays using IGFBP1-overexpressing and knockdown cell lines. The single-cell-RNA-sequence data indicated that IGFBP1 facilitates the progression of LUAD cells through the MAPK signaling pathway. Subsequently, western blot analysis was performed to validate these findings, while the ERK inhibitor U0126 was employed for cellular experiments and in vivo verification to elucidate the precise biological function of IGFBP1.

[RESULTS] IGFBP1 was identified as the most significant biomarker for lymph node metastasis risk through immunohistochemical and Cox regression analyses. Genetic overexpression and knock-down of IGFBP1 demonstrated its critical role in regulating proliferation, migration, and invasion in vitro. These effects were mediated through ERK pathway activation, as confirmed by both Western blot analysis and pharmacological inhibition with U0126 in a subcutaneous tumor model.

[CONCLUSIONS] IGFBP1 indicates the promotion of lymph node metastasis in LUAD by facilitating tumor proliferation, invasion, and migration through modulation of the MAPK-ERK signaling pathway. Our findings highlight IGFBP1 as a potential prognostic biomarker, though its therapeutic utility requires validation in preclinical models.