Mannose-6-phosphate/insulin-like growth factor II receptor expression and tumor development

Abstract

The mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF-IIR) is a multi-functional transmembrane glycoprotein whose major function is to bind and transport M6P-bearing glycoproteins from the trans-Golgi network or the cell surface to lysosomes. The cell surface M6P/IGF-IIR also bind and internalizes the insulin-like growth factor II. The receptor gene is considered a "candidate" tumor suppressor gene. The phenotypic consequences of loss of M6P/IGF-IIR through somatic mutation are potentially very complex since M6P/IGF-IIR has a number of roles in cellular physiology. Loss of function mutations in M6P/IGF-IIR gene could contribute to multi-step carcinogenesis. In the light of the multi-functional cellular potential roles of the M6P/IGF-IIR the purpose of this review is to highlight some recent data concerning its normal functions and the potential role of its loss in tumor pathophysiology with the aim to try to clarify the possible underlying mechanisms of its involvement in tumor development.