AREG

Amphiregulin (AREG), also known as schwannoma-derived growth factor, is a member of the epidermal growth factor (EGF) family that binds to the epidermal growth factor receptor (EGFR/ERBB1). This heparin-binding glycoprotein functions as a paracrine effector in epithelial cell proliferation, differentiation, and tissue repair through activation of MAPK and PI3K-AKT signaling pathways. AREG overexpression has been implicated in multiple malignancies including colorectal, breast, and non-small cell lung cancers, where it promotes tumor progression via autocrine/paracrine stimulation of EGFR. Emerging evidence also links aberrant AREG expression to inflammatory disorders such as asthma and inflammatory bowel disease. While current EGFR-targeted therapies (e.g., cetuximab) indirectly modulate AREG activity, direct therapeutic strategies against AREG itself remain investigational, with preclinical studies exploring neutralizing antibodies and transcriptional inhibitors. Paradoxically, AREG demonstrates protective roles in mucosal healing, highlighting its context-dependent biological duality.