JAG1 and colorectal carcinoma: To unequivocally demonstrate the function of Jag1-ICD in drug resistance, OXP-R and 5FU-R CRC cell lines were treated with GSIs with no effect on viability (Figures 4A, B); conversely, the U0126 compound, which is able to inhibit Erk activation, rapidly counteracts Jagged1 processing (Supplementary Figures 4A, B), increasing chemosensitivity to OXP and 5FU (Figures 4A, B).