MELTF Drives Lung Cancer Progression and Angiogenesis via HIF-1α-Mediated Activation of the VEGF Signaling Pathway

Lung cancer remains the leading cause of cancer-related mortality globally. Melanotransferrin (MELTF) is an oncogene overexpressed in multiple cancer types. Preliminary reports link MELTF to lung cancer progression, but its precise regulatory mechanisms remain undefined. This study aimed to elucidate MELTF's functional role in lung cancer and its underlying molecular pathways. Bioinformatic analyses and clinical tissue microarray assessments were first integrated to characterize MELTF's prognostic relevance. MELTF expression was quantified in cell lines and mouse models via quantitative real-time PCR (qRT-PCR) and Western blot. Cellular functional assays (CCK-8, colony formation, wound healing, transwell, flow cytometry, and tube formation) were employed to evaluate MELTF's impact on lung cancer cell malignant behaviors. Furthermore, the role of MELTF in vivo was validated in NSG mice models. Clinical tissue microarrays and qRT-PCR revealed MELTF overexpression in lung cancer tissues and cell lines, respectively. MELTF knockdown suppressed proliferation and migration while enhancing apoptosis in A549 and NCI-H1299 cells. In vivo mouse experiments and in vitro cell-based assays collectively demonstrated that MELTF promoted lung cancer progression by activating the vascular endothelial growth factor (VEGF) pathway, with hypoxia-inducible factor-1α (HIF-1α) serving as a key mediator of this regulatory axis. MELTF drove lung cancer progression by activating the VEGF signaling pathway via HIF-1α, identifying MELTF as a promising therapeutic target for lung cancer.