Crosstalk between Epidermal Growth Factor Receptors (EGFR) and integrins in resistance to EGFR tyrosine kinase inhibitors (TKIs) in solid tumors

Abstract

Cell adhesion to the extracellular matrix (ECM) is important in a variety of physiological and pathologic processes, including development, tumor invasion, and metastasis. Integrin-mediated attachment to ECM proteins has emerged to cue events primitively important for the transformed phenotype of human cancer cells. Cross-talk between integrins and growth factor receptors takes an increasingly prominent role in defining adhesion, motility, and cell growth. This functional interaction has expanded beyond to link integrins with resistance to Tyrosine kinase inhibitors (TKIs) of Epidermal Growth Factor Receptors (EGFRs). In this regard, integrin-mediated adhesion has two separate functions one as a clear collaborator with growth factor receptor signaling and the second as a basic mechanism contributing in Epithelial to Mesenchymal Transition (EMT) which affects response to chemotherapy. This review provides an overview of these mechanisms and describes treatment options for selectively targeting and disrupting integrin interaction to EGFR for cancer therapy.

Keywords: Epidermal Growth Factor Receptor (EGFR); Epithelial to Mesenchymal Transition (EMT); Integrin; Resistance; Tyrosine kinase inhibitors (TKIs).