PGK1 (Phosphoglycerate Kinase 1)

In fed-batch fermentation, SCC7 achieved 6972.8 mg/L COR in a 6 L bioreactor, representing the highest COR titer reported in S. cerevisiae to date. In conclusion, this study establishes an efficient yeast platform for COR production and provides a useful reference for biosynthesis of other bioactive nucleosides.

In conclusion, SIX5 functions as a critical oncogenic driver in GBM, regulated by KDM5C and promoting tumor progression through UBE2C-mediated activation of AKT/mTOR signaling and glycolytic reprogramming. The KDM5C-SIX5-UBE2C regulatory axis represents a potential prognostic biomarker and therapeutic target in glioblastoma.

Importantly, treatment with Eeyarestatin I, a small-molecule ER stress agonist, restored sunitinib sensitivity in tumor cells. These findings reveal a novel PABPC1-PGK1 regulatory axis underlying sunitinib resistance and suggest a promising therapeutic strategy for overcoming drug resistance in ccRCC.

Strikingly, VHL-deficient ccRCC exhibits greater on-target pathway sensitivity to dexamethasone at the H4K12la-glycolysis axis, and glucocorticoid dexamethasone potentiated the antitumor efficacy of the HIF-2α inhibitor belzutifan in both orthotopic cell line-derived and patient-derived xenograft models. Collectively, our findings establish H4K12la as a metabolic‒epigenetic amplifier in VHL-deficient ccRCC, reposition glucocorticoids as epigenetically active modulators that dampen lactate-driven chromatin activation and glycolytic output, and provide a mechanistically grounded combination strategy with HIF-2α blockade to target lactate-fueled transcriptional dependence in metabolically rigid tumors.

Inhibition of PGK1 initiates autophagy in T315I-mutant chronic myeloid leukemia (CML) cells, thereby enhancing their sensitivity to first-generation Tyrosine Kinase Inhibitor (TKI) imatinib and third-generation TKI ponatinib. Notably, CPU-216 induces autophagy via VCP and Beclin 1 in CML-T315I cells, enhancing their responsiveness to TKIs. These discoveries propose a novel therapeutic strategy for T315I-mutant CML, underscoring the potential to develop targeted treatments that leverage the kinase functions of PGK1.

Further, the endogenous ceramide species Cer(d18:1/26:0) destabilizes this complex, triggering PD-L1 lysosomal destruction and potentiating antitumor immunity. These findings delineate a ceramide-gated sorting mechanism within the endosomal network, revealing a druggable metabolic switch to disrupt immune evasion and amplify checkpoint blockade efficacy.

Genetic targeting of either PGK1 or SPP1 restored oxidative metabolism in Hypoxia-TAM, suppressed glioma invasiveness, and synergized with PDT to delay tumor growth and prolong survival in orthotopic models. Our findings reveal a PGK1-centered metabolic-paracrine axis in Hypoxia-TAM that drives PDT resistance, nominating this pathway as a promising therapeutic target for glioma.

Notably, all hub genes demonstrated strong diagnostic performance, highlighting their potential as sensitive biomarkers of glyphosate exposure. Collectively, this study provides comprehensive insights into gene expression changes associated with glyphosate exposure in hepatoma cells, linking them to hepatic metabolic dysregulation and immune modulation and suggesting a panel of hub genes with potential diagnostic and therapeutic significance.

CE acts as a potent radiosensitizer, augmenting γ-irradiation-induced apoptosis in A375 cells through metabolic disruption, oxidative stress modulation, intrinsic apoptotic activation, and cell cycle arrest. These results highlight its potential for improving melanoma radiotherapy. Future research should optimize dosing regimens and explore clinical translation to advance precision oncology strategies.

This work proposes a glycosylation-based risk model for predicting CCA prognosis and directing therapeutic strategies. PGK1 is highlighted as a potential therapeutic target in CCA.

Inhibition of PGK1 by CBR-470-1 prevented cardiac hypertrophy in cellular and animal models. Our findings highlight a critical role for PGK1 in myocardial hypertrophy, with downstream activation of the vimentin/PI3K/Akt/ferroptosis pathway.

We developed and validated a robust CCRG signature that effectively predicts prognosis, immune contexture, and therapeutic response in breast cancer. This signature offers novel insights into metabolic immunosuppression and provides a potential tool for risk stratification and personalized treatment strategies.