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

Small GTPases. 2018 Nov 2;9(6):457-464. doi: 10.1080/21541248.2016.1262935. Epub 2017 Jan 20.

Abstract

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.

Keywords: EGFR; MYC; autocrine signaling; kras; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autocrine Communication
  • Carcinogenesis*
  • ErbB Receptors / metabolism*
  • Humans
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Proto-Oncogene Proteins p21(ras) / metabolism*

Substances

  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)