The Epidermal Growth Factor Receptor (EGFR) is the prototypical receptor tyrosine kinase (RTK). These cell surface receptors are integral membrane proteins that bind ligands on their extracellular domain and relay that information to within the cell. The activated EGFR regulates diverse cell fates such as growth, proliferation, differentiation, migration, and apoptosis. These signaling properties are important for the appropriate development and maintenance of an organism. However, when inappropriately controlled, due to EGFR overexpression or hyperactivation, these signaling events are characteristic of many cancers. It remains unclear whether the uncontrolled EGFR activity leads to cell transformation or is a consequence of cell transformation. Regardless of the cause, increased EGFR activity serves both as a biomarker in the diagnosis of some cancers and is a molecular target for anti-cancer therapies. The promising results with current anti-EGFR therapies suggest that the receptor is a viable molecular target for a limited number of applications. However, to become an effective therapeutic target for other cancers that have elevated levels of EGFR activity, current approaches for inhibiting EGFR signaling will need to be refined. Here we describe the molecular mechanisms that regulate EGFR inactivation and discuss their potential as therapeutic targets for inhibiting EGFR signaling.
Keywords: EGFR; MVB; degradation; endocytosis.