Growth factors mediate their diverse biologic responses (regulation of cellular proliferation, differentiation, migration and survival) by binding to and activating cell-surface receptors with intrinsic protein kinase activity named receptor tyrosine kinases (RTKs).
About 60 RTKs have been identified and can be classified into more than 16 different receptor families. Their activity is normally tightly controlled and regulated. Overexpression of RTK proteins or functional alterations caused by mutations in the corresponding genes or abnormal stimulation by autocrine growth factor loops contribute to constitutive RTK signaling, resulting in alterations in the physiological activities of cells. The ErbB receptor family of RTKs comprises four distinct receptors: the EGFR (also known as ErbB1/HER1), ErbB2 (neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). ErbB family members are often overexpressed, amplified, or mutated in many forms of cancer, making them important therapeutic targets. EGFR has been found to be amplified in gliomas and non-small-cell lung carcinoma while ErbB2 amplifications are seen in breast, ovarian, bladder, non-small-cell lung carcinoma, as well as several other tumor types. Several data have shown that ErbB receptor family and its downstream pathway regulate epithelial-mesenchymal transition, migration, and tumor invasion by modulating extracellular matrix (ECM) components. Recent findings indicate that ECM components such as matrikines bind specifically to EGF receptor and promote cell invasion. In this review, we will present an in-depth overview of the structure, mechanisms, cell signaling, and functions of ErbB family receptors in cell adhesion and migration. Furthermore, we will describe in a last part the new strategies developed in anti-cancer therapy to inhibit ErbB family receptor activation.
Frontiers in pharmacology. 2015 Nov 24*** epublish ***
Aline Appert-Collin, Pierre Hubert, Gérard Crémel, Amar Bennasroune
UMR CNRS 7369, Unité Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne Reims, France. , Laboratoire d'Ingénierie des Systèmes Macromoléculaires, CNRS-AMU UMR 7255 Marseille, France. , INSERM U1109 MN3T Strasbourg, France. , UMR CNRS 7369, Unité Matrice Extracellulaire et Dynamique Cellulaire, Université de Reims Champagne-Ardenne Reims, France ; UMR CNRS 7360, Laboratoire Interdisciplinaire des Environnements Continentaux, Université de Lorraine Metz, France.