RAPGEF1 and neuroblastoma: In general, ALK activates multiple signaling pathways, such as the PI3K-AKT, CRKL-C3G, MEKK2/3-MEK5-ERK5, JAK-STAT and MAPK signaling pathways 19, which involved in the initiation and progression of many different cancer types, including lymphomas, neuroblastoma and colorectal cancer.