Oncogenic KRAS and the EGFR loop in pancreatic carcinogenesis-A connection to licensing nodes.

EGFR signaling has a critical role in oncogenic KRAS-driven tumorigenesis of the pancreas, whereas it is dispensable in other organs. The complex signaling network engaged by oncogenic KRAS and its modulation by EGFR signaling, remains incompletely understood. In order to study early signaling events activated by oncogenic KRAS in the pancreas, we recently developed a novel model system based on murine primary pancreatic epithelial cells enabling the time-specific expression of mutant KrasG12D from its endogenous promoter. Here, we discuss our findings of a KrasG12D-induced autocrine EGFR loop, how this loop is integrated by the MYC oncogene, and point to possible translational implications.