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Supplementary Figure 5 from Requirements for Aurora-A in Tissue Regeneration and Tumor Development in Adult Mammals

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posted on 2023-03-30, 21:49 authored by Ignacio Pérez de Castro, Cristina Aguirre-Portolés, Gonzalo Fernández-Miranda, Marta Cañamero, Dale O. Cowley, Terry Van Dyke, Marcos Malumbres

PDF file - 133KB, Characterization of Aurora-A null skin.

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ARTICLE ABSTRACT

Aurora-A is a kinase involved in the formation and maturation of the mitotic spindle and chromosome segregation. This kinase is frequently overexpressed in human cancer, and its activity may confer resistance to antitumoral drugs such as Taxol. Inhibition of Aurora-A results in mitotic defects, and this kinase is considered as an attractive therapeutic target for cancer. Nevertheless, the specific requirements for this kinase in adult mammalian tissues remain unclear. Conditional genetic ablation of Aurora-A in adult tissues results in polyploid cells that display a DNA-damage–like response characterized by the upregulation of p53 and the cell-cycle inhibitor p21Cip1. This is accompanied by apoptotic, differentiation, or senescence markers in a tissue-specific manner. Therapeutic elimination of Aurora-A prevents the progression of skin and mammary gland tumors. However, this is not due to significant levels of apoptosis or senescence, but because Aurora-A–deficient tumors accumulate polyploid cells with limited proliferative potential. Thus, Aurora-A is required for tumor formation in vivo, and the differential response observed in various tissues might have relevant implications in current therapeutic strategies aimed at inhibiting this kinase in the treatment of human cancer. Cancer Res; 73(22); 6804–15. ©2013 AACR.