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ANTONINO AGRUSA

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

  • Autori: Cammareri, P; Scopelliti, A; Todaro, M; Eterno, V; Francescangeli, F; Moyer, MP; Agrusa, A; Dieli, F; Zeuner, A; Stassi, G
  • Anno di pubblicazione: 2010
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: colorectal cancer stem cells
  • OA Link: http://hdl.handle.net/10447/51283

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.