PGK1 Is a Key Target for Anti-Glycolytic Therapy of Ovarian Cancer: Based on the Comprehensive Analysis of Glycolysis-Related Genes

Abstract

Reprogramming of energy metabolism is a key hallmark of cancer, which provides a new research perspective for exploring the development of cancer. However, the most critical target of anti-glycolytic therapy for ovarian cancer remains unclear. Therefore, in the present study, Oncomine, GEPIA, and HPA databases, combined with clinical specimens of different histological types of ovarian cancer were used to comprehensively evaluate the expression levels of glycolysis-related metabolite transporters and enzymes in ovarian cancer. We selected phosphoglycerate kinase 1 (PGK1), which showed the greatest prognostic value in the Kaplan-Meier Plotter database, for subsequent validation. Immunochemistry assays confirmed that PGK1 was highly expressed in ovarian cancer. The PGK1 expression level was an independent risk factor for the survival and prognosis of patients with ovarian cancer. Functional analysis showed that the PGK1 expression level was positively correlated with the infiltration of neutrophils. Cell experiments confirmed that inhibiting PGK1 expression in ovarian cancer cells could reduce the epithelial-mesenchymal transition (EMT) process, resulting in loss of cell migration and invasion ability. The small molecule NG52 dose-dependently inhibited the proliferation of ovarian cancer cells. In addition, NG52 reduced the EMT process and reversed the Warburg effect by inhibiting PGK1 activity. Therefore, PGK1 is an attractive molecular target for anti-glycolytic therapy of ovarian cancer.

Lysine Acetylation in the Proteome of Renal Tubular Epithelial Cells in Diabetic Nephropathy

“…Meanwhile, the combination of CREBBP and HIF-1α can also act on the downstream enzymes, such as Pgk1 (HG/NG: 0.744 at Kac388, 0.669 at Kac30, 0.702 at Kac291), Aldolase A (Aldoa, HG/NG: 1.496 at Kac230), and Hexokinase 2 (Hk2, HG/NG: 0.65 at Kac418) to promote anaerobic reactions and influence TGF-β-dependent fibrosis processes ( Ye et al, 2018 ; Yin et al, 2019 ). Interestingly enough, the increased acetylation level of PGK1 at K323 may promote its enzyme activity and exacerbate the EMT process in ovarian cancer cells ( Hu et al, 2017 ; Gou et al, 2021 ). Furthermore, as one of the downstream enzymes of HIF-1α, PDK-1 (HG/NG: 0.688AT Kac212) is known to be associated with apoptosis and the TCA cycle ( Saurus et al, 2015 ; Heinemann-Yerushalmi et al, 2021 ).…”

Gemcitabine–Paclitaxel Chemotherapy for Patients with Advanced Urothelial Cancer Refractory to Cisplatin-Based Chemotherapy: Predictive Role of PGK1 for Treatment Response to Cytotoxic Chemotherapy

“…Combined with clinical information, a biomolecular approach will help to facilitate a precision medicine approach for aUC. Recently, metabolic reprogramming proteins, especially PGK1, have been highlighted as an emerging hallmark of cancer, and our study had two striking findings in the analysis of PGK1 in aUC [ 25 , 26 ]. First, we separately evaluated the predictive role of PGK1 in cytoplasm and nucleus.…”

Pathological Role of Phosphoglycerate Kinase 1 in Balloon Angioplasty-Induced Neointima Formation

“…In addition, a short-term intervention targeting early response genes (e.g., PGK1) could also provide a similar efficacy at preventing restenosis as long-term drug release. To date, numerous PGK1 blockers, such as CBR-470-1, NG52, and GQQ-792, have been developed as potential anti-cancer drugs with inhibitory mechanisms on tumor growth, metastasis, the epithelial-mesenchymal transition process, as well as chemotherapy resistance [51][52][53]. However, it is largely unknown whether these PGK1 inhibitors or their derivatives can be applied for preventing neointimal formation.…”