Growth factor receptors (GFR) activation spark different pathways, such as RAS/MAPK and PI3K/AKT/mTOR, activity and turn on transcriptional regulators, such as JUN/FOS/EGR1, that drive cell division, promote sarcoma cell proliferation, tissue organization and trophicity, and boost sarcomagenesis [36]. Here, RAPGEF5 is linked to sarcoma.