Tumor-Derived Polyamines Initiate Fat Wasting in Cancer Cachexia
Fabregat, M.; Fenske, R. J.; Hansen, J. K.; Kaminsky, C. J.; Lortie, J.; Nassar, A.; Kressin, K.; Jen, A.; Cilloni, L.; Overmeyer, K.; Alexander, C. M.; Garrett, J. W.; Pickhardt, P. J.; Coon, J. J.; Lyssiotis, C. A.; Pasca di Magliano, M.; Li, L.; Kuchnia, A. J.; Galmozzi, A.
Show abstract
Cancer-associated cachexia (CC) is a fatal metabolic condition characterized by progressive loss of fat and muscle mass, yet its early molecular drivers remain poorly defined. Here, we identify a polyamine-dependent tumor-adipose crosstalk that triggers adipocyte lipolysis and fat wasting during the pre-cachexia stage, preceding systemic inflammation and muscle atrophy. Cancer-derived polyamines are enriched in extracellular vesicles and promote lipid mobilization via eIF5A hypusination, independent of adrenergic signaling. In preclinical models, polyamine accumulation associates with early fat loss and elevated circulating fatty acids. Clinically, automated CT imaging of newly diagnosed pancreatic cancer patients reveals increased adipose density, reflecting lipolysis, that correlates with circulating polyamine levels and predicts poor survival. These findings support polyamine metabolism as a mechanistic driver and candidate biomarker of early cachexia, providing a framework for early detection and targeted intervention.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and -independent mitophagy 96%
- Therapeutic targeting of SLC6A8 creatine transporter inhibits KRAS mutant and wildtype colon cancer and modulates human creatine levels 96%
- In-vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma 96%
Similar papers in this journal
- DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis 96%
- Multi-omic Characterization of Pancreatic Cancer-Associated Macrophage Polarization Reveals Deregulated Metabolic Programs Driven by the GMCSF-PI3K Pathway 96%
- Robust single nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity 96%
Similar papers in this journal
- Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer 96%
- The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/beta-catenin to RTK/MAPK signaling 95%
- NF2 loss malignantly transforms human pancreatic acinar cells and enhances cell fitness under environmental stress 95%
Similar papers in this journal
- C/EBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer 96%
- Loss of Bone Morphogenetic Protein-binding Endothelial Regulator Causes Insulin Resistance 96%
- Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer 96%
Similar papers in this journal
- Electron transport inhibition increases cellular dependence on purine transport and salvage 95%
- Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia 95%
- Targeting pathogenic Lafora bodies in Lafora disease using an antibody-enzyme fusion 95%
"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.