Supplementary Figure 2A shows that GSI compounds induce a rapid release of the Jag1-ICD fragment, strictly linked to Erk activation in CRC cells. Accordingly, the MEK inhibitor U0126 abrogates Jagged1 processing and the addition of GSIs restores the Jag1-ICD accumulation, after washing out of Erk inhibition (Supplementary Figure 2B). Here, JAG1 is linked to colorectal carcinoma.