PGK1 mediates glycolysis and cell proliferation in endometriosis by regulating DDIT4 nuclear translocation.

Endometriosis (EM), a gynecologic disorder affecting 10 % of childbearing age women, with complex pathogenesis involving cell proliferation and metabolic abnormalities similar to malignancies. Unusual expression of key enzymes and regulators in glycolysis pathway contributes to the development of endometriosis. Phosphoglycerate kinase 1 (PGK1) was a key enzyme in glycolysis with additional roles as a transcription factor co-activator and protein kinase. We discovered that PGK1 was elevated and associated strongly with the development of EM. The PGK1 inhibitor NG52 inhibited the growth of endometriosis lesions in mice by preventing cell migration and proliferation. Furthermore, we found that DNA damage response 4 (DDIT4) was a new downstream target gene of PGK1. PGK1 regulated the nuclear translocation of DDIT4. Additionally, we also observed that PGK1 up-regulate the transcriptional activity of DDIT4, leading to DDIT4 overexpression that promoted the development of endometriosis. These findings may provide new insights for potential non-hormonal targeted therapies for endometriosis treatment.