Epidermal growth factors are small protein molecules that are involved in cell signalling pathways. These signalling proteins play a crucial role in regulating fundamental cellular processes like cell growth, proliferation, differentiation and survival. In the human body, epidermal growth factors act through binding to receptor tyrosine kinases on the cell surface and trigger intracellular signalling cascades. Aberrant expression and regulation of epidermal growth factors market have been linked to various disease conditions including cancer. This article aims to provide an overview of epidermal growth factors, their mechanisms of action and physiological roles.

What are Epidermal Growth Factors?

Epidermal growth factors refer to a family of proteins that were originally identified from an extract of male mouse submaxillary glands. The founding member and namesake of this family is epidermal growth factor (EGF). Some other well-studied epidermal growth factors include transforming growth factor alpha (TGF-α), amphiregulin, heparin-binding EGF (HB-EGF), betacellulin and epiregulin. These low molecular weight proteins share considerable amino acid sequence homology, especially in the cysteine-rich domain that is crucial for receptor binding.

EGFs act through activation of ErbB receptor tyrosine kinases present on the cell surface. In humans, these receptors include EGFR/ErbB1, ErbB2, ErbB3 and ErbB4. Binding of EGF ligands to these receptors triggers dimerization and autophosphorylation of intracellular tyrosine kinase domains. This leads to downstream signaling via MAPK, PI3K/Akt and other pathways to regulate gene expression responses governing cell proliferation, survival and differentiation.

Roles of EGF in Physiology and Disease

EGF and other family members play vital roles during embryonic development, tissue repair, wound healing and homeostasis in adult tissues. For example, EGF is essential for normal epidermal development and hair follicle morphogenesis. EGF signaling mediated through EGFR regulates intestinal epithelial cell proliferation, survival, migration and differentiation important for gut renewal and repair. Deregulated EGF signaling is implicated in various disease processes as well.

Cancer: Aberrant activation of EGF receptors due to gene overexpression, mutations or autocrine stimulation leads to uncontrolled cell proliferation in many epithelial cancers including lung, breast, pancreatic, head and neck cancers. Anti-EGFR therapies targeting EGFR mutations have shown survival benefits in lung cancer patients.

Wound Healing: EGF topical application or enhanced signaling accelerates re-epithelialization and wound closure. However, excessive EGF activity can also promote aberrant scarring and fibrosis.

Other Roles: Roles for EGF signaling have been shown in processes like neurite outgrowth, synaptic plasticity, bone development, cardiac protection and kidney development/repair. Dysregulated EGF signaling contributes to conditions like psoriasis.

EGF Signaling Crosstalk and Complexity

The cellular responses to EGF stimulation are complex due to interactions with other signaling networks. For example, EGFR transactivates Platelet-derived growth factor receptors and vice versa augmenting their downstream signals. Additionally, EGFs show functional redundancy as different ligands can activate the same ErbB receptors with varying affinities. Signaling outcomes also depend on expression levels and heterodimerization patterns of ErbB receptors. Post-translational modifications of receptors and cross-regulation by micro-RNAs add further complexity. Together, these factors determine the spatial-temporal dynamics and context-specific functions of EGF signaling in physiology and disease.

Future Directions

Understanding the multifaceted nature of EGF signaling continues to provide opportunities for therapeutic interventions. Developing isoform-selective EGFR inhibitors minimizes off-target toxicities seen with pan-ErbB inhibitors. Combination strategies targeting EGFR along with downstream nodes or parallel pathways offer better efficacy. In cancers showing primary resistance to EGFR inhibitors, predictive biomarkers help identify alternative treatment approaches. Biomechanical cues from the tumor microenvironment that impinge on EGF signaling also need attention. Expanding our knowledge of EGF signaling networks in normal development and homeostasis will aid management of wound healing and other disorders as well. Overall, basic research continues unraveling new regulatory layers of EGF signaling with potential for improved clinical applications.

Conclusion

To summarize, epidermal growth factors market are an evolutionarily conserved family of glycoproteins that play central roles in cell growth, differentiation and survival through activation of ErbB receptor tyrosine kinases. Aberrant EGF signaling contributes to pathogenesis of epithelial cancers and other diseases. Understanding the complex signaling networks and context-specific functions of EGFs provides opportunities to develop more effective targeted therapies.