Interestingly, our preliminary study also showed that TGF-β in the EVs was not alerted in ITGBL1 overexpressing or silencing CRC cells (Supplementary Fig. 20a), and their effect on TGF-β/Smads signaling pathway was little in the targeted HCT116 cells and CAFs from liver metastatic tumors (Supplementary Fig. 20b, c). The gene discussed is ITGBL1; the disease is metastatic neoplasm.