The Insulin-like Growth Factor II/Mannose 6-Phosphate Receptor: Implications for IGF Action in Breast Cancer

The insulin-like growth factors, particularly IGF-II, interact with multiple cell surface receptors. One of these receptors, the insulin-like growth factor II/mannose 6-phosphate receptor (IGF2R, also called the Type II IGF receptor), has a structure distinct from IGF1R or the insulin receptor. While IGF2R binds IGF-II with high affinity, it also serves as a cell surface receptor for many other proteins relevant to breast cancer biology. As such, IGF2R could play a role in several different key cellular functions including IGF-II action, lysosome biogenesis, and regulation of several novel ligands. These possibilities, along with the intriguing demonstration of loss of heterozygosity at the IGF2R locus, provide clues that this receptor could have an important function in breast cancer. This review will discuss potential ways that IGF2R could influence breast cancer biology.