EGFR Signaling Pathway

Epidermal growth factor (EGF) was first discovered in newborn rats in 1962. After about 20 years, the human epidermal growth factor receptor (EGFR) was isolated and purified. As research progresses, EGFR and its downstream pathways are constantly understood. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (PKB, also known as Akt) signaling pathway is a downstream pathway of EGFR that is dysregulated in most human tumors. EGFR mainly stimulates the Ras protein after dimerization, which leads to the phosphorylation cascade and activates the PI3K/Akt signaling pathway, which causes tumorigenesis and development. Therefore, some scholars call it EGFR/PI3K/Akt signaling pathway. It has been confirmed that there are abnormal expression and dysfunction of EGFR in various malignant tumor tissues and tumor cell lines, including bladder cancer, ovarian cancer, nasopharyngeal carcinoma, breast cancer, glioblastoma, pancreatic cancer, prostate cancer, esophageal cancer and so on.

Studies have found that inactivation of PTEN inevitably leads to activation of the PI3K/Akt pathway, which is also the result of EGFR overexpression or mutation. Moreover, activated Akt has a variety of biological activities, which can promote the growth and proliferation of tumor cells through cascade phosphorylation of a series of proteins. It can also inhibit apoptosis, promote invasion and metastasis, regulate tumor angiogenesis, and tolerate tumor treatment. It can be seen that the dysregulation of EGFR/PI3K/ Akt signaling pathway is closely related to the occurrence and development of tumors.