Authors' Affiliations: Cellular and Molecular Oncology, Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Salvatore Maugeri, Pavia, Italy; Departments of Surgical and Oncological Sciences, Biopathology and Biomedical Methodologies, and GENURTO, University of Palermo, Palermo, Italy; Department of Hematology and Oncology, Istituto Superiore di Sanita, Rome, Italy; and INCELL Corporation, San Antonio, Texas.
Cancer Res. 2010 May 11.
Colorectal cancer stem cells (CR-CSC) are responsible for the generation and maintenance of intestinal tumors and are highly resistant to conventional chemotherapeutic agents. Aurora-A, a serine-threonine kinase involved in mitosis regulation, plays multiple key functions in tumor initiation and progression. We found that Aurora-A is overexpressed in primary colorectal tumor cells, in the CR-CSC fraction, and in stem cell-derived differentiated cells, compared with normal colon tissue. Aurora-A expression was functionally linked to centrosome amplification in CR-CSC, as indicated by the decrease in cells with multiple centrosomes that followed Aurora-A silencing. Knockdown of Aurora-A resulted in growth inhibition of CR-CSC, alteration of cell cycle kinetics, and downregulation of the expression levels of antiapoptotic Bcl-2 family members, strongly sensitizing to chemotherapy-induced cell death. Moreover, Aurora-A silencing compromised the ability to form tumor xenografts in immunocompromised mice and reduced the migratory capacity of CR-CSC. Altogether, these results indicate that Aurora-A is essential for CR-CSC regeneration and resistance to cytotoxic stimuli and suggest that therapies directed against Aurora-A may effectively target the stem cell population in colorectal cancer. Cancer Res; 70(11); OF1-11. (c)2010 AACR.
PMID: 20460511 [PubMed - as supplied by publisher] Source: National Library of Medicine.
