法国国家健康与医学研究所的研究人员日前发现,有两种基因在癌细胞的扩散中发挥了重要作用,这一发现将为寻找癌症治疗方法提供新的思路。
该研究所的一个研究小组7月11日发表公报说,人体含有名为Twist1和Twist2的两种基因,它们是胚胎发育的“主要调控因子”,但在正常成年人体内它们一般都选择“沉默”。不过研究人员通过实验发现,在很多癌症病例当中,这两种基因又重新被激活,它们能够增强癌细胞侵略性和活动性,使其越过免疫系统的“防线”,向其他器官扩散。
研究小组的负责人阿兰·皮叙认为,这一发现将有助于尽早发现恶性肿瘤以及研究癌症的早期疗法,该研究成果已刊登在最新一期美国《癌细胞》(Cancer Cell)杂志上。(生物谷Bioon.com)
生物谷推荐原始出处:
Cancer Cell,Vol 14, 79-89, 08 July 2008,Stéphane Ansieau, Alain Puisieux
Induction of EMT by Twist Proteins as a Collateral Effect of Tumor-Promoting Inactivation of Premature Senescence
Stéphane Ansieau,1 Jeremy Bastid,1,2,6 Agnès Doreau,1,6 Anne-Pierre Morel,3,6 Benjamin P. Bouchet,1,2 Clémence Thomas,1,2 Frédérique Fauvet,3 Isabelle Puisieux,1 Claudio Doglioni,4 Sara Piccinin,5 Roberta Maestro,5 Thibault Voeltzel,1 Abdelkader Selmi,1,2 Sandrine Valsesia-Wittmann,1 Claude Caron de Fromentel,1 and Alain Puisieux1,2,3,
1 Inserm, U590, Lyon, F-69008, France
2 Université de Lyon, Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques, Lyon, F-69008, France
3 Centre Léon Bérard, FNCLCC, Laboratoire de Recherche Translationnelle, Lyon, F-69008, France
4 Belluno City Hospital, Belluno, I-32100, Italy
5 CRO IRCCS, Aviano National Cancer Institute, Aviano, I-33081, Italy
Summary
Twist1 and Twist2 are major regulators of embryogenesis. Twist1 has been shown to favor the metastatic dissemination of cancer cells through its ability to induce an epithelial-mesenchymal transition (EMT). Here, we show that a large fraction of human cancers overexpress Twist1 and/or Twist2. Both proteins override oncogene-induced premature senescence by abrogating key regulators of the p53- and Rb-dependent pathways. Twist1 and Twist2 cooperate with Ras to transform mouse embryonic fibroblasts. Interestingly, in epithelial cells, the oncogenic cooperation between Twist proteins and activated mitogenic oncoproteins, such as Ras or ErbB2, leads to complete EMT. These findings suggest an unanticipated direct link between early escape from failsafe programs and the acquisition of invasive features by cancer cells.