Intriguingly, the level of extracellular vesicle-TβRII (EV-TβRII) secreted by the metastatic breast cancer cells markedly increased upon TGF-β treatment in Hrs-dependent manner, whereas the cellular levels decreased (Fig. 1h and Supplementary Fig. 1g, h), which suggests that after TGF-β stimulation cell surface TβRII is not simply directed for degradation by internalization, but instead secreted into TEVs. This evidence concerns the gene TGFB1 and breast cancer.