Kras/ADAM17-dependent Jag1-ICD reverse signalling sustains CRC progression and chemoresistance
Colorectal cancer (CRC) is characterized by well-known genetic defects and about 50% of the cases harbour oncogenic RAS mutations. Increased expression of Notch-ligand Jagged1 occurs in several human malignancies, including CRC, and correlates with cancer progression, poor prognosis and recurrence. Herein, we demonstrate that Jagged1 is constitutively processed in CRC tumours with mutant Kras, ultimately triggering an intrinsic reverse signalling via its nuclear-targeted intracellular domain (Jag1-ICD).