Review on EGFR-ERK1/2 signaling cascade: implications on cell proliferation in health and disease

Abstract

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is often increased in malignancies such as non–small cell lung cancer, metastatic colorectal cancer, head and neck cancer, pancreatic cancer, and breast cancer. EGFR activity may be enhanced by different ways. These include typical mutations and truncations in the extracellular domain, and in the kinase domain. Overactivation of downstream ERK1/2 signaling pathway occurs as a result of these EGFR abnormalities. Cancer cell proliferation is aided by the chronic start and advancement of the cell cycle, which is triggered once these pathways are activated. This article discusses the ligand-binding and dimerization molecular processes that control EGFR signal transmission and its relationship to the ERK1/2 signaling axis that forces cells toward the G1 phase of the cell cycle. Furthermore, it illustrates how EGFR signaling pathways promote cyclin D expression via ERK1/2 activation.