Tumor-Derived Polyamines Initiate Fat Wasting in Cancer Cachexia.

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 wit

SUBMITTER: Fabregat M 

PROVIDER: S-EPMC12900250 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature