Our data provides evidence on FBXW7 as a critical tumor suppressor mutated and inactivated in melanoma that results in sustained NOTCH1 activation and renders NOTCH signaling inhibition as a promising therapeutic strategy in this setting.

Adaptor or scaffolding proteins mediate protein-protein interactions that drive the formation of protein complexes. GAB2 scaffolding protein is an intermediary molecule that links plasma membrane receptor signaling including receptor tyrosine kinases with the downstream effectors such as SHP2, p85 subunit of PI3K, PLCγ, CRK, SHC and SHIP. Although well described in signal transduction, its role in cancer has recently been emerging especially in leukemia, breast and ovarian cancer, and melanoma. GAB2 is essential for two major signal transduction pathways in cancer, thePI3K-AKT and ERK signaling pathways, and thus regulates a number of key cellular processes. This review focuses on structure and function of GAB2, its regulatory proteins, emerging role in cancer, and potential as a therapeutic target.