Article

Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis

Division of Molecular Medicine, Rudjer Bosković Institute, Zagreb, Croatia.
Cancer letters (Impact Factor: 5.62). 08/2009; 289(1):11-22. DOI: 10.1016/j.canlet.2009.06.036
Source: PubMed

ABSTRACT The cation-independent mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is a multifunctional receptor. It is involved in a variety of cellular processes which become dysregulated in cancer. Its tumor suppressor role was recognized a long time ago. However, due to its multifunctionality, it is not easy to understand the extent of its relevance to normal cellular physiology. Accordingly, it is even more difficult understanding its role in carcinogenesis. This review presents critical and focused highlights of data relating to M6P/IGF2R, obtained during more than 25 years of cancer research.

0 Followers
 · 
116 Views
  • Source
    ChemBioChem 03/2011; 12(5):685-90. DOI:10.1002/cbic.201000785 · 3.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin-like growth factor-II (IGF-II) is a key regulator of cell growth, survival, migration and differentiation, and is thus pivotal in many cancers. An individual with a high IGF-II level is at high risk of developing cancer, whereas IGF2R is implicated as being important in tumor suppression. Thus, uncovering the essence of the IGF-II/IGF2R interaction is very important to understanding the origin of the tumor-suppressing effect of IGF2R. In this study, in order to investigate the interaction of the IGF-II/IGF2R complex and to characterize the binding hot spots of this interaction, a 10 ns molecular dynamics simulation combined with MM-PBSA/MM-GBSA computations and computational alanine scanning was performed on the IGF-II/IGF2R complex. From the results of the free-energy decomposition and the computational alanine scanning calculation, we identified the key residues in the IGF-II/IGF-2R interaction. The results from the calculation were consistent with reported experimental mutagenesis studies. The information on the interaction of IGF-II and IGF2R obtained is vital for understanding how the structure of IGF2R influences the function of IGF-II in growth and development. This study will also lead to new opportunities to develop molecular probes that can assist in diagnostic screening, and even novel approaches to controlling tumor development.
    Journal of Molecular Modeling 07/2011; 18(4):1421-30. DOI:10.1007/s00894-011-1159-4 · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Insulin-like growth factor-II (IGF-II) affects many aspects of cellular function through its ability to activate several different receptors and, consequently, numerous intracellular signalling molecules. Thus, IGF-II is a key regulator of normal foetal development and growth. However, abnormalities in IGF-II function are associated with cardiovascular disease and cancer. Here, we review the cellular mechanisms by which IGF-II's physiological and pathophysiological actions are exerted by discussing the involvement of the type 1 and type 2 IGF receptors (IGF1R and IGF2R), the insulin receptor and the downstream MAP kinase, PI-3 kinase and G-protein-coupled signalling pathways in mediating IGF-II stimulated cellular proliferation, survival, differentiation and migration.
    Growth factors (Chur, Switzerland) 12/2011; 30(1):1-12. DOI:10.3109/08977194.2011.640325 · 3.09 Impact Factor
Show more