EGF receptor in organ development, tissue homeostasis and regeneration
Top Cited Papers
Open Access
- 19 February 2025
- journal article
- review article
- Published by Springer Nature in Journal of Biomedical Science
- Vol. 32 (1) , 1-33
Abstract
The epidermal growth factor receptor (EGFR) is a protein embedded in the outer membrane of epithelial and mesenchymal cells, bone cells, blood and immune cells, heart cells, glia and stem neural cells. It belongs to the ErbB family, which includes three other related proteins: HER2/ErbB2/c-neu, HER3/ErbB3, and HER4/ErbB4. EGFR binds to seven known signaling molecules, including epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α). This binding triggers the formation of receptor pairs (dimers), self-phosphorylation of EGFR, and the activation of several signaling pathways within the cell. These pathways influence various cellular processes like proliferation, differentiation, migration, and survival. EGFR plays a critical role in both development and tissue homeostasis, including tissue repair and adult organ regeneration. Altered expression of EGFR is linked to disruption of tissue homeostasis and various diseases, among which cancer. This review focuses on how EGFR contributes to the development of different organs like the placenta, gut, liver, bone, skin, brain, T cell regulation, pancreas, kidneys, mammary glands and lungs along with their associated pathologies. The involvement of EGFR in organ-specific branching morphogenesis process is also discussed. The level of EGFR activity and its impact vary across different organs. Factors as the affinity of its ligands, recycling or degradation processes, and transactivation by other proteins or environmental factors (such as heat stress and smoking) play a role in regulating EGFR activity. Understanding EGFR’s role and regulatory mechanisms holds promise for developing targeted therapeutic strategies.Keywords
Funding Information
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN_2022 Prot. 2022WB59LB, PRIN_2022PNRR Prot. P2022C948R, NextGenerationEU” DD. 3175/2021 E DD. 3138/2021 CN_3)
This publication has 258 references indexed in Scilit:
- TheEGF/EGFRaxis and its downstream signaling pathways regulate the motility and proliferation of cultured oral keratinocytesFEBS Open Bio, 2023
- Loss of EGFR contributes to high‐fat diet‐induced nonalcoholic fatty liver diseaseFEBS Letters, 2023
- Cross‐talk between EGFR and BMP signals regulates chondrocyte maturation during endochondral ossificationDevelopmental Dynamics, 2021
- TGF‐β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathwaysMolecular Oncology, 2017
- Emerging functions of the EGFR in cancerMolecular Oncology, 2017
- Combined systemic elimination of MET and epidermal growth factor receptor signaling completely abolishes liver regeneration and leads to liver decompensationHepatology, 2016
- Dissecting the role of epidermal growth factor receptor catalytic activity during liver regeneration and hepatocarcinogenesisHepatology, 2015
- Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in miceHepatology, 2013
- Transforming growth factor α suppression of articular chondrocyte phenotype and Sox9 expression in a rat model of osteoarthritisArthritis & Rheumatism, 2007
- Epidermal Growth Factor (Nobel Lecture)Angewandte Chemie International Edition, 1987