GALNT7-induced O-glycosylation of NUP50 activates fatty acid β-oxidation to promote lung adenocarcinoma metastasis.

Lung adenocarcinoma (LUAD) is a common and highly metastatic subtype of lung cancer. Despite its high prevalence, the molecular pathways underlying its metastatic potential remain poorly elucidated. Here, we revealed increased GALNT7 expression and Tn antigen levels in LUAD tissues. Using a series of CCK-8, Transwell, and Western blot assays, we demonstrated that GALNT7 knockdown effectively inhibited LUAD cell proliferation, migration, and invasion, while also mitigating epithelial-mesenchymal transition and reducing metastasis-associated protein levels. In contrast, GALNT7 overexpression exacerbated these phenotypes. Mechanistically, GALNT7 colocalized with NUP50 at the nuclear envelope and enhanced the O-glycosylation of NUP50, thereby stabilizing the protein and activating fatty acid β-oxidation pathways, which are critical for LUAD cell metastasis. Knockdown of GALNT7 disrupted this pathway, markedly inhibiting metastasis. In vivo, using nude mouse xenograft and lung metastasis models, we confirmed that GALNT7 overexpression can synergize with NUP50-WT to significantly promote tumor growth and metastasis, while also enhancing the levels of NUP50 and VVA. In contrast, supplementation with NUP50-MUT effectively blocked the tumor-promoting effects of GALNT7 overexpression. In summary, this study systematically dissects the role of GALNT7 in LUAD metastasis, revealing key mechanisms that could inform the development of new therapeutic strategies and potential drug targets.