Mannose-6-Phosphate/Insulin-Like Growth Factor 2 Receptor (M6P/IGF2-R) in Growth and Disease: A Review

Abstract

This work aims to summarize the current knowledge about Mannose-6-Phosphate/Insulin-like Growth Factor 2 Receptor (M6P/IGF-2R) in the regulation of growth and development, and its involvement in tumor progression. M6P/IGF2-R binds both molecules sharing M6P signals and IGF2. The studies showed that M6P/IGF2-R is involved in the traffciking of mannose-6-phosphorylated enzymes from the Trans Golgi Network (TGN) to lysosomes and the uptake of secreted proenzymes from the plasma membrane to the lysosomes via clathrin-coated vesicles for their maturation. The M6P/IGF-2R acts as a scavenger that binds IGF2 and transports it to lysosomes for its degradation since IGF2 exerts its biological effects on cell proliferation and development by binding with lower affinity on IGF1 receptor, which is structurally similar to insulin receptor and different from the M6P/IGF2-R. The M6P/IGF2-R has also been studied in human cancer, and frequent losses of heterozygosity (LOH) at the 6p25-27 gene region with mutations in the remaining allele has been described. These results led to consider M6P/IGF2-R gene as a putative tumor suppressor and its potential prognostic value has been suggested.