Epidermal growth factor receptor kinase substrate 8 (EPS8)

Epidermal growth factor receptor kinase substrate 8 (EPS8) is a multifunctional adaptor protein that plays a critical role in integrating growth factor signaling with actin cytoskeleton dynamics [UniProt Q12929, PMID: 21636681]. Originally identified as a substrate for the EGFR tyrosine kinase, it contains several functional domains, including a PTB domain, an SH3 domain, and a C-terminal actin-binding region [PMID: 10847611]. EPS8 functions as part of a ternary complex with SOS1 and ABI1, which exhibits guanine nucleotide exchange factor (GEF) activity specific for the Rho-family GTPase Rac, thereby promoting actin remodeling and cell migration [PMID: 10847611, PMID: 15107404]. In addition to its role in Rac activation, EPS8 can directly regulate actin filaments through capping and bundling activities, which are essential for the formation of filopodia and lamellipodia [PMID: 15107404]. In the context of human disease, EPS8 is frequently overexpressed in a variety of solid tumors, including oral, breast, and pancreatic cancers, where it correlates with increased metastatic potential and poor clinical outcomes [PMID: 21636681, PMID: 25605116]. Consequently, EPS8 is considered a promising therapeutic target for inhibiting cancer cell invasion and metastasis [PMID: 25605116]. While specific small-molecule inhibitors are still in the early stages of development, strategies targeting its SH3 domain or its interaction with signaling partners have shown potential in preclinical models [PMID: 21636681].

Other names

EPS8Epidermal growth factor receptor pathway substrate 8

Inhibition of the EPS8-ABI1-SOS1 complex to prevent Rac activation and disruption of actin-capping and bundling activities to inhibit cell motility.