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.
Interactions between cells or between cell and substratum involve specificreceptors and their ligands. Among the various cell surface receptorsidentified during the last decades, the carbohydrate-binding proteins, e.g., lectins are of peculiar interest because glycolipids, glycoproteinsand proteoglycans have been shown to interact with lectins on the surfaceof animal cells. Animal lectins are recognized as molecules playingimportant roles in a variety of biological processes through binding toglycoconjugates and lectin-like receptors such as selectins, sialoadhesins(CD22, CD33), natural killer receptors (NKR-P1, CD69 and CD94/NKG2), hyaluronate receptors (CD44, RHAMM, ICAM-1), B-cell associated antigen(CD23, CD72), γ2 leukocyte integrin (CD11b/CD18) or the well-knownreceptors for mannose, mannose-6-phosphate or asialoglycoprotein havebeen suggested to be able to mediate the transfer of information fromthe outside to the inside of the cell. This review focuses on the mostrecent advances in our understanding of the molecular basis of “outside-in” signaling mediated by lectins. Lectin-likereceptors are involved in signal transduction in a great variety of ways;at the molecular level, they mimic in most of the cases the function ofgrowth factor receptor either coupled to tyrosine kinase activity or toheterotrimeric G protein. They lead to a multiplicity of cellular eventsfollowing their activation depending on factors such as cellular type, species and/or tissue. Nevertheless the potential of surface lectins astransducers is emphasized by the observation that in a few cases lectin-likereceptors induce either novel signal transduction mechanism or newintracellular events with regards to what it has been observed as aconsequence of growth factor receptor activation. This observation bringsthe idea that lectins may offer, as cell surface transducers, an alternativeor additional signaling potential to cell.