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Cancer Cell. 2004 Dec;6(6):625-30.

Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells.

Author information

1
INSERM U590, Centre Léon Bérard, Université Claude Bernard Lyon 1, Lyon F-69008 France.

Abstract

N-Myc oncogene amplification is a frequent event in neuroblastoma and is strongly correlated with advanced disease stage and treatment failure. Similarly to c-Myc oncogenic activation, N-Myc deregulation promotes both cell proliferation and p53-dependent apoptosis by sensitizing cells to a variety of insults. Intriguingly, p53 mutations are uncommon in neuroblastomas, strongly suggesting that an alternative cooperating event circumvents this safeguard against oncogene-driven neoplasia. By performing a pangenomic cDNA microarray analysis, we demonstrate that human Twist is constantly overexpressed in N-Myc-amplified neuroblastomas. H-Twist overexpression is responsible for the inhibition of the ARF/p53 pathway involved in the Myc-dependent apoptotic response. This oncogenic cooperation of two key regulators of embryogenesis causes cell transformation and malignant outgrowth.

PMID:
15607966
DOI:
10.1016/j.ccr.2004.09.033
[Indexed for MEDLINE]
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