AMPK suppresses multiple cell death pathways to sustain tumor-associated macrophage proportion and promotes tumor progression

This part depends on their capacity to resist cell death by adapting to the harsh tumor microenvironment, characterized by nutrient deprivation and the accumulation of metabolic waste, through metabolic reprogramming. This enables TAMs to not only utilize excess metabolites and metabolic waste in the tumor microenvironment as energy sources, but also to cope with metabolic stress by upregulating cysteine uptake and activating hypoxia-inducible factors, thereby maintaining their survival and function.

However, the core genes that suppress TAM death in response to the metabolic dynamics of the tumor microenvironment during tumor progression remain unknown. In this study, we used proteomics analysis combined with experimental validation found that the degree of TAM apoptosis decreased while the level of AMPK activation increased during tumor progression. Notably, myeloid-specific knockout of AMPK significantly inhibits tumor growth, reduces TAM proportion in the tumor, and weakens its pro-tumor phenotype.