Aurora-A Is Essential for the Tumorigenic Capacity and Chemoresistance of Colorectal Cancer Stem Cells

作者：Cammareri Patrizia; Scopelliti Alessandro; Todaro Matilde; Eterno Vincenzo; Francescangeli Federica; Moyer Mary Pat; Agrusa Antonino; Dieli Francesco; Zeuner Ann; Stassi Giorgio^*

来源：Cancer Research, 2010, 70(11): 4655-4665.

DOI：10.1158/0008-5472.CAN-09-3953

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); 4655-65.

• 出版日期2010-6-1