2025/02/27 by Qionghua Cui, Shijin Li, Xidan Liu +9 · 1 voice
Immunology and Microbiology · Medicine · Neuroscience · #Macrophage Migration Inhibitory Factor #GDF15 and Related Biomarkers #Nuclear Receptors and Signaling
paper · doi:10.1016/j.cmet.2025.01.018
openalex publication_date 2025/02/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Both exercise and cancer can cause adipose tissue shrinkage. However, only cancer-associated weight loss, namely cachexia, is characterized by profound adipose inflammation and fibrosis. Here, we identified tumor-secreted macrophage migration inhibitory factor (MIF) as a major driver that skews the differentiation of adipose stem and progenitor cells (ASPCs) toward a pro-inflammatory and pro-fibrogenic direction, with reduced adipogenic capacity in cancer cachexia. By contrast, circulating MIF is moderately reduced after exercise. Mechanistically, atypical chemokine receptor 3 (ACKR3) in ASPCs serves as the predominant MIF receptor mediating its pathological effects. Inhibition of MIF by gene ablation in tumor cells or pharmacological blockade, as well as ASPC-specific Ackr3 deficiency, markedly alleviates tumor-induced cachexia. These findings unveil MIF-ACKR3 signaling as a critical link between tumors and cachectic manifestations, providing a promising therapeutic target for cancer cachexia.