[Cancer cells escape from failsafe programs in a simple Twist].
A major obstacle to the expansion of abnormal cells with significant proliferative potential is the induction of either cellular senescence or 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. This observation provides a mechanistic explanation for the rarity of p53 mutations in neuroblastomas. It also highlights the involvement of two crucial regulators of embryogenesis in human cancer development. In this review, we discuss the possible role of Twist 1 in tumour progression, based on the numerous recent studies reporting its overexpression in a variety of human cancers.
Unité Inserm 590, Centre Léon Bérard, 28, rue Laennec, 69008 Lyon. puisieux@lyon.fnclcc.fr
Alain
A
Puisieux
Sandrine
S
Valsesia-Wittmann
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016922:Cellular Senescence / Q000502:physiology; D002648:Child; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000502:physiology; D005784:Gene Amplification / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics* / Q000556:secondary; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000502:physiology*
D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; C103173:TWIST1 protein, human; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1