MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy.

摘要: Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and represents an attractive target for the development anticancer drugs. Similarly, elevated protein O-GlcNAcylation O-GlcNAc transferase (OGT) are detected various cancers serve as novel cancer-specific therapeutic targets. However, potential connection between them remains unexplored. Here, a positive correlation was found activated hyper-O-GlcNAcylation cancer types inhibition by 10 µM U0126 significantly decreased expression OGT H1299, BPH-1 DU145 cells; then, pathway analysis regulators obtained from UCSC Genome Browser done, ten downstream targets ERK were uncovered; following results showed that ELK1, one pathway, mediated signaling-induced upregulation; finally, MTT assay soft agar reduced promotion effect on cell proliferation anchorage-independent growth. Taken together, our data originally provided evidence regulatory mechanism tumors, which will be helpful drugs targeting to hyper-O-GlcNAcylation. This study also new signaling-enhanced malignancy. Altogether, recently discovered oncogenic factor linked classical essential maintenance malignant phenotype cancers.