title: The centrosome: a target for cancer therapy.
abstract: The centrosome plays an essential role in cell cycle progression and cell polarity, organizing the microtubule network in interphase and mitosis. During cell division, the centrosome undergoes a series of structural and functional transitions and forms the two poles of the bipolar mitotic spindle. It is the microtubule cytoskeleton that is reorganized to form the two poles, ensuring accurate separation of the two daughter cells. To achieve this a large number of signalling proteins located at the centrosome, undergo precise time-dependent modulation. Protein kinases such as Aurora A, Polo and Neks, trigger and regulate events such as centrosome duplication, maturation and division. These enzymes are also involved in recruiting other proteins in cell division, thus they are likely to mediate the crosstalk between the cell and the centrosome cycle. In its function of microtubule organization, macromolecular complexes also have an important role. Tubulin polymerization confers the structural backbone to cell division, while other proteins may interact with it and/or mediate its recruitment to the centrosome. The interactions of these components regulate centrosome maturation and microtubule growth, essential mechanisms for cell division. Furthermore, dysregulation of this organelle, both at the level of signalling or as a structural element strongly correlates to aberrant proliferation, and the onset of tumours. Therefore, the centrosome represents an attractive target for anti-cancer therapy. Here we review the most important centrosomal proteins and their therapeutic potential. In addition, we summarize the current strategies of intervention and report the present stage of anti-cancer drug development targeting the centrosome.
authors.affiliation: Macromolecular Crystallography Group, Structural Biology and Biocomputing Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Mazzorana
authors.forename: Guillermo
authors.initials: G
authors.lastname: Montoya
authors.forename: Gulnahar B
authors.initials: GB
authors.lastname: Mortuza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents