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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4655-4665
Number of pages11
JournalCancer Research
Volume70
Issue number11
DOIs
Publication statusPublished - Jun 1 2010

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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