Whereas TGF-β-induced cancer progression is a well-established concept, it is reported that non-invasive cancer cells exhibit a weaker responsiveness to TGF-β that is insufficient to drive metastasis.10 Further, low TGF-β signaling levels are often explained by prompt signaling termination following endocytosis and proteasome/lysosome degradation of the TGF-β receptors complexes.47,48 In this study, we show that hyperactivation of TGF-β signaling in invasive cancer cells is caused by accelerated secretion and uptake of sEVs containing TGF-β activity. This evidence concerns the gene TGFB1 and cancer.