PGM3 inhibition Shows cooperative Effects With Erastin inducing Pancreatic cancer cell death via activation of the Unfolded Protein Response
Zerbato, B.; Gobbi, M.; Ludwig, T.; Brancato, V.; Pessina, A.; Brambilla, L.; Wegner, A.; Chiaradonna, F.
Show abstract
1Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor patient prognosis. Remarkably, PDAC is one of the most aggressive and deadly tumor types and is notorious for its resistance to all types of treatment. PDAC resistance is frequently associated with a wide metabolic rewiring and in particular of the glycolytic branch named Hexosamine Biosynthetic Pathway (HBP). Here we show the effect of the combined treatment between an HBPs Phosphoglucomutase 3 (PGM3) enzyme inhibitor, named FR054, and erastin (ERA), a recognized ferroptosis inducer, on PDAC cell growth and survival. Noteworthy, the combined treatment applied to PDAC cell lines induces a significant decrease in cell proliferation and a concurrent enhancement of cell death. Furthermore, we show that this combined treatment induces Unfolded Protein Response (UPR), NFE2 Like BZIP Transcription Factor 2 (NRF2) activation, a change in cellular redox state, a greater sensitivity to oxidative stress, a major dependence on glutamine metabolism, and finally ferroptosis cell death. Our study discloses that HBP inhibition enhances, through UPR activation, the ERA effect and therefore might be a novel anticancer mechanism to be exploited as PDAC therapy.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Deficiency of DDI2 suppresses liver cancer progression byworsening cell survival conditions 95%
- PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells 94%
- DNA damage and oxidizing conditions activate p53 through differential upstream signaling pathways. 94%
Similar papers in this journal
- Low level of antioxidant capacity biomarkers but not target overexpression predicts vulnerability to ROS-inducing drugs 96%
- Discovery of decreased ferroptosis in male colorectal cancer patients with KRAS mutations 95%
- Amino acid restriction sensitizes lung cancer cells toferroptosis via GCN2-dependent activation of the integratedstress response 95%
Similar papers in this journal
- Mitophagy contributes to alpha-tocopheryl succinate toxicity in GSNOR-deficient hepatocellular carcinoma. 95%
- Discovery of a AhR flavonoid agonist that counter-regulates ACE2 expression in rodent models of inflammation and attenuates ACE2-SARS-CoV2 interaction in vitro 94%
- Ribosomal protein L5 (RPL5/uL18) I60V mutation is associated to increased translation and modulates drug sensitivity in T-cell acute lymphoblastic leukemia cells 93%
Similar papers in this journal
- NDR2 Kinase Regulate Microglial Metabolic Adaptation and Inflammatory Response: Critical Role in Glucose-Dependent Functional Plasticity 95%
- A proteomic study of the dual oncogenic and tumor- suppressive roles of SIRT3 in lung and breast cancer cell lines 94%
- H19 is a PERK-regulated long non-coding RNA that fine-tunes UPR signalling and inhibits endoplasmic reticulum stress-induced cell death 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.