Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells.

Francesco Dieli, Giorgio Stassi, Antonino Agrusa, Matilde Todaro, Patrizia Cammareri, Federica Francescangeli, Alessandro Scopelliti, Vincenzo Eterno, Mary Pat Moyer, Giorgio Stassi, Ann Zeuner, Patrizia Cammareri, Alessandro Scopelliti, Vincenzo Eterno

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Abstract

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.
Lingua originaleEnglish
pagine (da-a)4655-4665
Numero di pagine11
RivistaCancer Research
Volume11
Stato di pubblicazionePublished - 2010

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Dieli, F., Stassi, G., Agrusa, A., Todaro, M., Cammareri, P., Francescangeli, F., Scopelliti, A., Eterno, V., Moyer, M. P., Stassi, G., Zeuner, A., Cammareri, P., Scopelliti, A., & Eterno, V. (2010). Aurora-a is essential for the tumorigenic capacity and chemoresistance of colorectal cancer stem cells. Cancer Research, 11, 4655-4665.