RasGRP1 opposes proliferative EGFR–SOS1–Ras signals and restricts intestinal epithelial cell growth

Philippe Depeille1,6, Linda M. Henricks1,5, Robert A. H. van de Ven1,5, Ed Lemmens1,5, Chih-Yang Wang1,2, Mary Matli3, Zena Werb1, Kevin M. Haigis4, David Donner3, Robert Warren3 and Jeroen P. Roose1,6

The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome.