Control of EGFR signaling by endocytosis and endosomal trafficking

Epidermal growth factor receptor (EGFR) is a critical regulator of cell proliferation, survival, and differentiation. In many types of cancers, overexpression or overactivation of EGFR correlates with cancer progression, metastasis, and worse prognosis. Therefore, anti-EGFR therapies have been developed to treat cancers by inhibiting the EGFR activation and by blocking the EGFR-mediated downstream signaling. As a receptor tyrosine kinase, EGFR is activated by binding with its ligands at the cell surface. Then, the subsequent membrane trafficking events such as endocytosis, recycling, and endosome to lysosome trafficking tightly control the EGFR activation levels and downstream signaling. Here, we provide a snapshot on the current knowledge of the EGFR membrane trafficking processes, the important regulators of EGFR trafficking, the EGFR mutations disturbing normal membrane trafficking, and the connection between EGFR trafficking with cancer resistance to anti-EGFR therapies.