Pro-oncogenic roles of apoptotic caspases

凋亡半胱天冬酶的促癌作用

基本信息

批准号：
8702585
负责人：
Chuan-Yuan Li
金额：
$ 35.33万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-08 至 2019-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Apoptosis is normally considered a barrier for carcinogenesis because of its roles in getting rid of unwanted or damaged cells. However recent discoveries in our laboratory suggest that we need to re-examine the roles of apoptosis, especially those of apoptotic caspases, in carcinogenesis. In this project, we will examine the hypothesis that non-lethal caspase 3 or 7 activation induces genomic instability to facilitate radiation and other stress-induced carcinogenesis. Our hypothesis is a bold one that goes against the current paradigm. It will have wide-ranging implications since many endogenous and external stimuli could activate apoptotic caspases. Examples of such stimuli include exposure to ionizing radiation, UV, chemicals, and oncogene expression (e.g., myc). A facilitative role for caspases in carcinogenesis would provide exciting new insights into how those diverse environmental insults cause cancer. We will use a variety of in vitro and in vivo models, in combination with state-of-the-art molecular technologies, to examine the roles of caspases 3&7 in radiation- and other stress-induced genetic instability and carcinogenesis. We expect our studies to provide a comprehensive evaluation of the roles of caspases 3&7 in promoting carcinogenesis through inducing genetic instability. Upon completion of the project, we hope we can gain significant insights into the roles of apoptotic caspases in carcinogenesis. Such insights may provide novel targets for future cancer prevention strategies.

描述（由申请人提供）：凋亡通常被认为是癌变的障碍，因为它在摆脱不需要或受损的细胞中的作用。但是，我们实验室的最新发现表明，我们需要重新检查凋亡的作用，尤其是凋亡胱天蛋白酶的作用，在致癌作用中。在该项目中，我们将研究以下假设：非致命caspase 3或7激活诱导基因组不稳定性促进辐射和其他应激诱导的癌变。我们的假设是反对当前范式的大胆假设。它将具有广泛的含义，因为许多内源性和外部刺激都可以激活凋亡的caspase。这种刺激的例子包括暴露于电离辐射，紫外线，化学物质和癌基因表达（例如Myc）。胱天蛋白酶在致癌作用中的促进作用将为那些多样化的环境侮辱引起癌症提供令人兴奋的新见解。我们将使用各种体外和体内模型，结合最先进的分子技术，以检查caspases 3和7在放射线和其他应激诱导的遗传不稳定性和癌变中的作用。我们预计我们的研究将对胱天蛋白酶3和7通过诱导遗传不稳定促进致癌作用的作用进行全面评估。该项目完成后，我们希望我们能够对凋亡caspase在致癌作用中的作用有重大见解。这些见解可能为未来的预防癌症预防策略提供新的目标。