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The ErbB receptors and their ligands in cancer: an overview
N Normanno1, C Bianco, L Strizzi
1Cell Biology and Preclinical Models Unit, INT-Fondazione Pascale, 80131 Naples, Italy. nicnorm@yahoo.com
Abstract:
This review article provides an overview on the most recent advances on the role of ErbB receptors and growth factors of the epidermal growth factor (EGF)-family of peptides in cancer pathogenesis and progression. The ErbB tyrosine kinases and the EGF-like peptides form a complex system. In fact, the interactions occurring between receptors and ligands of these families affect the type and the duration of the intracellular signals that derive from receptor activation. Interestingly, activation of ErbB receptors is also driven by different classes of membrane receptor, suggesting that ErbB kinases can amplify growth promoting signals carried by different pathways. The importance of ErbB receptors and EGF-like peptides in development of organs and tissues has been demonstrated by using different mouse models. In vitro and in vivo studies have also shown that ErbB receptors and their ligands can act as transforming genes. However, evidence suggests that cooperation of different receptors and ligands is necessary to induce a fully transformed phenotype. Indeed, co-expression of different ErbB receptors and EGF-like growth factors is a common phenomenon in human primary carcinomas. This observation suggests that the growth and the survival of carcinoma cells is sustained by a network of receptors/ligands of the ErbB family. In this respect, the contemporary expression of different ErbB tyrosine kinases and/or EGF-like growth factors in human carcinomas might also affect tumor response to target based agents directed against the ErbB receptor/ligand system.
Insights
ErbB receptors and epidermal growth factor (EGF)-family peptides are crucial in cancer. Their complex interactions drive cancer growth and may influence treatment response, highlighting a network sustaining carcinomas.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The epidermal growth factor receptor (EGFR) or ErbB family comprises four receptor tyrosine kinases (ErbB1-4).
- ErbB receptors and their ligands, the epidermal growth factor (EGF)-family peptides, play vital roles in normal development and tissue homeostasis.
- Dysregulation of the ErbB system is implicated in various human cancers.
Purpose of the Study:
- To review recent advances in understanding the role of ErbB receptors and EGF-family peptides in cancer.
- To explore the complex signaling network involving ErbB receptors and their ligands in cancer pathogenesis and progression.
- To discuss the implications of ErbB system dysregulation for tumor development and therapeutic strategies.
Main Methods:
- Review of recent scientific literature on ErbB receptors, EGF-family peptides, and cancer.
- Analysis of in vitro and in vivo studies, including mouse models and human carcinoma data.
- Examination of signaling pathways and molecular interactions within the ErbB network.
Main Results:
- ErbB receptors and EGF-like peptides form a complex system where interactions influence intracellular signaling duration and type.
- ErbB receptor activation can be amplified by other membrane receptors, integrating signals from diverse pathways.
- Co-expression of multiple ErbB receptors and EGF-like growth factors is common in human carcinomas, suggesting a collaborative network sustaining tumor growth and survival.
- The ErbB network's complexity may impact tumor response to targeted therapies.
Conclusions:
- The ErbB receptor/ligand system is a critical driver of cancer pathogenesis and progression.
- A complex network of ErbB receptors and EGF-like growth factors sustains carcinoma cell growth and survival.
- Understanding this network is essential for predicting and improving responses to targeted cancer therapies.
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