Anastasis, a new mechanism driving cell survival and evolution

Anastasis，驱动细胞生存和进化的新机制

基本信息

批准号：
8932673
负责人：
Denise J. Montell
金额：
$ 76.75万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
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：
2014-09-24 至 2019-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): We recently discovered a new biological phenomenon, which we call anastasis (Greek for "rising to life"). Overturning the current dogma that cell death is irreversible, we found that a variety of normal and cancer cell types can reverse the process, survive, and proliferate. This reversibility takes place even after cells experience events widely believed to be points of no return, including activation of caspase enzymes and widespread DNA damage. Notably, while most cells fully recover and repair their damaged DNA, some cells retain mutations, and this increases the frequency of oncogenic transformation. The discovery of anastasis has at least five paradigm-shifting implications. First, we suggest that anastasis represents a previously unknown cause of cancer, so inhibiting anastasis should prevent cancer. Anastasis could also offer an explanation for the longstanding observation that repeated injury increases the incidence of cancer. Second, we propose that anastasis allows tumor cells to escape chemotherapy and evolve drug resistance. Therefore, inhibiting anastasis may enhance the effectiveness of chemo- and radiation therapies and prevent relapses. Third, salvaging cells on the brink of death via anastasis may limit permanent tissue injury due to transient environmental stresses or toxin exposures. Consequently, enhancing anastasis may promote tissue regeneration. Fourth, we posit that anastasis is a cell survival mechanism that protects cells that are difficult to replace such as neurons in the adult brain or heart muscle cells, so promoting anastasis could prevent or slow degenerative diseases. Fifth, we propose that the survival of germ cells with mutations acquired through anastasis provides a mechanism to enhance genetic diversity precisely when animals are exposed to stressful environmental conditions. This could accelerate adaptation to changing environments during evolution. Here we propose to test these ideas. We designed a biosen

描述（由申请人提供）：我们最近发现了一种新的生物学现象，我们称之为Anastasis（希腊语“升级为生命”）。推翻了当前细胞死亡不可逆的教条，我们发现各种正常和癌细胞类型可以扭转过程，生存和增殖。即使在细胞经历广泛认为是无回报的点之后，这种可逆性也发生，包括激活caspase酶和广泛的DNA损伤。值得注意的是，尽管大多数细胞完全恢复并修复受损的DNA，但一些细胞保留了突变，这会增加致癌转化的频率。 anastasis的发现至少具有五个范式转移含义。第一的，我们建议阿纳斯塔斯代表以前未知的癌症原因，因此抑制吻合应预防癌症。阿纳斯塔症还可以为长期观察结果提供解释，即反复损伤会增加癌症的发生率。其次，我们建议anastasis允许肿瘤细胞逃脱化学疗法并进化耐药性。因此，抑制吻合可能会增强化学和辐射疗法的有效性并防止复发。第三，由于瞬时环境应力或毒素暴露，通过厌氧粉的边的挽救细胞可能会限制永久性组织损伤。因此，增强吻合可能会促进组织再生。第四，我们认为阿纳斯塔症是一种细胞存活机制，可保护难以替代的细胞，例如成人大脑或心脏肌肉细胞中的神经元，因此促进吻合可以预防或缓慢的退化性疾病。第五，我们提出，通过厌氧菌获得的突变的生殖细胞的存活提供了一种机制，可以在动物暴露于压力的环境条件下精确增强遗传多样性。这可以加速对进化过程中不断变化的环境的适应。在这里，我们建议测试这些想法。我们设计了一个biosen