C3 and breast cancer: This metabolic reprogramming leads to an increase in lactate secretion by CAFs, and the lactate is then metabolized by cancer cells to produce nicotinamide adenine dinucleotide, ultimately supporting cancer cell proliferation.[44] In breast cancer, C3a/C3aR signaling activates the PI3K/Akt pathway, leading to increased metastatic cytokine secretion and extracellular matrix generation by CAFs, ultimately facilitating tumor metastasis.[45]