Hepatic ceramide synthesis links systemic inflammation to organelle dysfunction in cancer.

ABSTRACT: Paraneoplastic syndromes arise when tumor-derived cytokines reprogram distant organs. Although mediators such as Interleukin-6 have been implicated, how these signals impair host organ function remains incompletely defined. Here, we identify a cytokine-lipid axis that drives hepatic autophagy dysfunction. Specifically, in Drosophila, the gut tumor-derived interleukin-like cytokine Upd3 induces the expression of the triglyceride lipase CG5966, which we named "cancer-associated lipid mobilizer (calm)", and the ceramide synthase schlank in the fat body. This upregulation rewires fat body lipid metabolism, resulting in an autophagic-flux blockade. Genetic reduction of either CG5966 or schlank restores organelle homeostasis and mitigates paraneop

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12621733 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature