fig3

Figure 3. Senescence promotes tumor metastasis through local and systemic microenvironmental reprogramming. The senescent TME generates multiple metastasis-promoting signals. These include pro-metastatic senescence-associated secretory phenotype (SASP) factors, such as IL-8, TGF-β, CXCL chemokines and MMPs; stress-adaptation pathways, e.g., integrated stress response (ISR)-ATF4-lipocalin 2 (LCN2) signaling; extracellular vesicles, and metabolic alterations involving lactate, fructose and methylmalonic acid (MMA).