DDB1 promotes pituitary adenoma progression by enhancing PAK1-mediated aerobic glycolysis.

DNA damage binding protein 1 (DDB1), a substrate receptor of CUL4-DDB1 E3 ligase, is overexpressed in various cancers and acts as a tumor promoting factor. However, the role of DDB1 in the metabolism of pituitary adenoma (PA) remains unclear. Here, we found that DDB1 was upregulated in PA tissues, and silencing DDB1 significantly inhibited the proliferation, cell cycle, prolactin (PRL) secretion and aerobic glycolysis in PA cells, whereas DDB1 overexpression had the opposite effect. We also confirmed that the co-localization and interaction of DDB1 and PAK1 using Co-IP and dual immunofluorescence experiments. Further analysis of cell functions showed that PAK1 knockdown or 2DG treatment reversed the effect of DDB1 overexpression on proliferation, cell cycle, PRL secretion, aerobic glycolysis, and apoptosis in PA cell lines. Importantly, we observed that overexpression of DDB1 in vivo promoted tumor growth in xenograft mice, which could be reversed by knockout of PAK1. In short, DDB1 promotes PA tumor growth and PRL secretion by enhancing PAK1-mediated aerobic glycolysis. Our results reveal that targeting the DDB1/PAK1 axis may provide a potential therapeutic strategy for PA.