GAPDH overexpression

GAPDH showed excellent predictive value in estimating the efficacy of immunotherapy and 11 anti-tumor drugs (e.g., cisplatin) (P<0.05), using TIDE and pRRophetic algorithms on the TCGA and GSE41613 datasets...Inhibiting GAPDH reversed these effects under all oxygen concentrations (P<0.05). Overall, our findings reveal GAPDH as a key hypoxia-related player influencing tumor progression, prognosis, and therapeutic potential in HNSCC.

The genosensor was applied to human samples by immunocapturing the exosomes directly from serum from breast cancer patients and showed a higher electrochemical signal (3.3-fold, p < 0.05), when compared with healthy controls, suggesting an overexpression of GAPDH on serum-derived exosomes from breast cancer patients. The detection of GAPDH transcripts is performed from only 1.0 mL of human serum using specific magnetic particles, improving the analytical simplification and avoiding ultracentrifugation steps, demonstrating to be a promising strategy for minimal invasive liquid biopsy.

Moreover, TKTL1 knockdown impedes hypoxia-induced transcription of genes encoding key enzymes and transporters involved in glucose, PPP and amino acid metabolism, rendering cells unable to switch to enhanced glycolysis under hypoxia. Altogether, our results show that TKTL1 plays a key role in the metabolic adaptation to hypoxia in THP-1 AML cells through modulation of G6PD and GAPDH activities, both regulating glucose/glutamine consumption and the transcriptomic overexpression of key players of PPP, glucose and amino acids metabolism.

Isotope tracing studies indicated that GADPHS mediates this shift through changes in pyruvate carboxylase activity and aspartate synthesis, both metabolic pathways critical for cancer survival and metastasis. Together these data identify a short isoform of GAPDHS that limits melanoma metastasis and regulates central carbon metabolism.

Importantly, SOX10 abrogation suppressed in vivo tumor growth and proliferation. Collectively, the results reveal that GAPDHS, which is regulated by SOX10, controls glycolysis and contributes to UM tumorigenesis, highlighting its potential as a therapeutic target.