RAB10 mediates metabolic regulation of ferroptosis in breast Cancer and synergistically remodels the tumour immune microenvironment via macrophage M2 polarization.

This study aimed to investigate the multifaceted biological functions of RAB10 in the development and progression of breast cancer, with a specific focus on its role and molecular mechanisms in remodelling the tumour metabolic and immune microenvironments. Experimental results demonstrated that RAB10 promotes the expression of PPARγ and its downstream target gene DGAT1 via activation of the PI3K/AKT signalling pathway. This axis drives lipid metabolic reprogramming and inhibits ferroptosis, thereby enhancing breast cancer cells survival under stress. The functional state of RAB10 modulates the tumour microenvironment via tumour-derived exosomes. Upon uptake by macrophages, these exosomes transmit signals that promote M2 polarization and inhibit ferroptosis. Crucially, knocking down RAB10 inhibits PPARγ via the PI3K/AKT pathway, thereby blocking M2 polarization of tumour-associated macrophages and enhancing CD8 T cell infiltration, thus reversing the immunosuppressive microenvironment. This study investigates the potential role of the RAB10/PI3K/AKT/PPARγ axis in remodelling the breast cancer microenvironment from the perspective of metabolic-immune crosstalk. These findings not only enhance the understanding of the interplay between metabolism and immune responses in the tumour microenvironment but also provide a potential theoretical foundation and novel research directions for combination treatment strategies targeting this pathway.