Epiregulin

Epiregulin (EREG) is a member of the epidermal growth factor (EGF) family of signaling proteins. It is produced as a transmembrane precursor that can be cleaved to release a soluble ligand. Epiregulin binds to members of the ErbB receptor family, principally the epidermal growth factor receptor (EGFR/ErbB1) and ErbB4, where it promotes receptor activation and downstream signaling.

EREG is expressed in multiple tissues, including skin, placenta, the gastrointestinal tract, and reproductive organs. Its expression is regulated during development and tissue repair and can be influenced by hormonal signaling. Epigenetic mechanisms, such as promoter methylation, can modulate its expression in cancer cells.

Mechanistically, binding of epiregulin to EGFR or ErbB4 induces receptor dimerization and activation, triggering signaling cascades such as MAPK/ERK and PI3K/AKT. These pathways promote cell proliferation, migration, and differentiation, enabling autocrine and paracrine effects that contribute to tissue growth and repair.

In physiology, epiregulin participates in development and wound healing, contributing to skin homeostasis and organogenesis. In cancer, EREG is frequently overexpressed and has been linked to tumor progression in several cancer types, including colorectal, breast, ovarian, and lung cancers. In colorectal cancer, higher EREG expression has been associated with better responses to anti-EGFR therapies in patients with RAS wild-type tumors, suggesting potential as a predictive biomarker. Ongoing research examines its role in therapy resistance and its potential as a therapeutic target within the EGFR signaling axis.