Ras-induced senescence and its physiological relevance in cancer.
Ras-induced senescence and its physiological relevance in cancer.
复制标题
DOI：
10.2174/156800910793357998
复制
发表时间：
2010-12
影响因子：
3
通讯作者：
David G
中科院分区：
文献类型：
--
作者：
Dimauro T;David G
由于像 Ras 这样的激活癌基因传统上被认为能够促进无限制的增殖，因此癌基因诱导衰老的概念一直存在争议，而且仍然存在争议。使用原代成纤维细胞中激活的 Ras 异位表达的体外研究最初推动了癌基因的激活会阻止细胞增殖的反直觉观念。虽然这些初步研究明确证明了离体系统中致癌基因诱导的新型细胞衰老的存在，但人们对该过程的生理相关性提出了疑问。事实上，小鼠癌症模型的最新技术进展表明，Ras 诱导的衰老的发生高度依赖于细胞环境以及激活 Ras 的表达水平，并且可能与人类癌症发生和/或进展的研究无关。然而，我们对细胞衰老分子基础的了解不断增加，使我们能够更好地了解体内调节癌症进展的分子事件。最近的研究不仅明确了肿瘤前病变中细胞衰老的发生率，而且还确定了其作为体内潜在肿瘤抑制机制的作用。在这里，我们回顾了最近关于 Ras 诱导衰老的生理相关性的令人兴奋的新发现，并讨论了它们对癌症治疗的影响。
Because activated oncogenes like Ras have traditionally been thought as promoting unrestrained proliferation, the concept of oncogene-induced senescence has been, and still is, controversial. The counter-intuitive notion that activation of oncogenes leads to the prevention of cellular proliferation has initially been fueled by in vitro studies using ectopic expression of activated Ras in primary fibroblasts. While these initial studies demonstrated unambiguously the existence of a new type of cellular senescence, induced by oncogenes in an ex-vivo system, questions were raised about the physiological relevance of this process. Indeed, recent technical advances in mouse modeling for cancer have suggested that the occurrence of Ras-induced senescence is highly dependent on the cellular context, as well as the level of expression of activated Ras, and may not be pertinent to the study of human cancer initiation and/or progression. However, our increased knowledge of the molecular basis for cellular senescence has led to a better understanding of the molecular events modulating cancer progression in vivo. Recent studies have not only clearly established the incidence of cellular senescence in pre-neoplasic lesions, but also its role as a potential tumor-suppressor mechanism in vivo. Here, we review the recent and exciting new findings regarding the physiological relevance of Ras-induced senescence, and discuss their implications in terms of cancer therapy.
登录
查看更多内容
影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
影响因子：
64.8
作者：
Di Micco, Raffaella;Fumagalli, Marzia;di Fagagna, Fabrizio d'Adda
通讯作者：
di Fagagna, Fabrizio d'Adda
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
7.7
作者：
Augert, Arnaud;Payre, Christine;Bernard, David
通讯作者：
Bernard, David
影响因子：
10.5
作者：
Barradas, Marta;Anderton, Emma;Gil, Jesus
通讯作者：
Gil, Jesus