¹INSERM U590 Centre Léon Bérard, Université Claude Bernard Lyon 1, 69373 Lyon Cedex 08, France

Correspondence: Dr A Puisieux, E-mail: puisieux@lyon.fnclcc.fr

Received 22 August 2005; Revised 25 October 2005; Accepted 25 October 2005; Published online 22 November 2005.

Abstract

A major obstacle to the expansion of abnormal cells with significant proliferative potential is the induction of programmed cell death. Consequently, oncogene-driven hyperproliferation must be associated with apoptosis inhibition to allow malignant outgrowth. The oncogenic cooperation of N-Myc and Twist-1 in the development of neuroblastoma, the most common and deadly solid tumour of childhood, perfectly illustrates such a process. N-Myc promotes cell proliferation, whereas Twist-1 counteracts its pro-apoptotic properties by knocking-down the ARF/p53 pathway. On the basis of numerous recent studies reporting its overexpression in a variety of human cancers, we discuss in this review the role of Twist-1 as a potent inhibitor of the cell safety programs engaged in response to an abnormal mitogenic activity.