Fig. 7: Schematic of the O-GlcNAcylation-POM121-c-MYC-ECM axis promoting bone metastasis in NSCLC.

Elevated O-GlcNAcylation of POM121 in bone-metastatic cells antagonizes ubiquitination by impairing binding to the E3 ubiquitin ligase TRIM21, thereby increasing POM121 protein stability. As a stabilized core NPC component, POM121 facilitates nuclear import of the oncogenic transcription factor c-MYC. Nuclear c-MYC subsequently drives transcription of ECM-related genes, promoting bone metastasis in NSCLC.