The complex biology of the receptor for the insulin-like growth factor-1

The receptor for the insulin-like growth factor-1 (IGF-1R) controls a wide variety of cellular functions. IGF-1R is a tyrosine kinase receptor that is activated by the binding of a ligand to the extracellular domain. There are three ligands for IGF-1R: IGF-I, IGF-II and insulin at supraphysiological concentrations. The binding of the ligand activates the catalytic activity of the tyrosine kinase domain, which in turn causes the autophosphorylation of IGF-1R. As a consequence of autophosphorylation, the activated IGF-1R sends a potent mitogenic signal to the cell nucleus. It has been clearly shown that an overexpressed and activated IGF-1R is quasi-obligatory for the establishment of a malignant cell phenotype. Interestingly, the targeting of IGF-1R can reverse the malignant phenotype in cancer cells, without affecting the biology of normal cells. For these reasons, IGF-1R seems to be a very promising candidate target for cancer therapy. In addition, IGF-1R protects cells from apoptosis and promotes cell growth and proliferation. However, more recent studies have also shown that IGF-1R regulates cell adhesion and motility, and, in certain cellular contexts, can induce differentiation. Indeed, the biology of the IGF-1R appears more complex than previously thought. The goal of this review is to describe the multiple functions displayed by IGF-1R in cell biology.