[Inactivation of failsafe programs by Twist oncoproteins and tumor progression].
Multicellular organisms have developed innate defense mechanisms to prevent the expansion of abnormal cells with significant proliferative potential. The two major safeguard mechanisms are premature senescence, which is characterized by definitive cell cycle arrest, and apoptosis, the most common form of programmed cell death. In normal and premalignant cells, the control of these processes is coupled to the regulation of cell proliferation, mainly through the p16 (Ink4A) -Rb and ARF-p53 intracellular signaling pathways. Hence, in benign tumors, aberrant mitogenic activity is counterbalanced by the induction of these oncosuppressive pathways, leading to either apoptosis or senescence which both limit tumor outgrowth. Progression towards malignant and potentially metastatic tumors requires the inhibition of these failsafe programs. Based on our work on Twist oncoproteins, we propose a presentation of recent data on cellular mechanisms by which cancer cells override the surveillance machinery and escape senescence and apoptosis, and we will describe the biological impact of this process on tumor metastasis.
Puisieux
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U590, Inserm, Lyon, France. puisieux@lyon.fnclcc.fr
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005784:Gene Amplification / Q000502:physiology; D016259:Genes, myc; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000502:physiology*; D018631:ras Proteins / Q000502:physiology
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; D018631:ras Proteins