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Is cancer a disease set up by cellular stress responses?
Cell Stress and Chaperones ( IF 3.3 ) Pub Date : 2021-05-24 , DOI: 10.1007/s12192-021-01214-4
Armando Aranda-Anzaldo 1 , Myrna A R Dent 1
Affiliation  

For several decades, the somatic mutation theory (SMT) has been the dominant paradigm on cancer research, leading to the textbook notion that cancer is fundamentally a genetic disease. However, recent discoveries indicate that mutations, including “oncogenic” ones, are widespread in normal somatic cells, suggesting that mutations may be necessary but not sufficient for cancer to develop. Indeed, a fundamental but as yet unanswered question is whether or not the first step in oncogenesis corresponds to a mutational event. On the other hand, for some time, it has been acknowledged the important role in cancer progression of molecular processes that participate in buffering cellular stress. However, their role is considered secondary or complementary to that of putative oncogenic mutations. Here we present and discuss evidence that cancer may have its origin in epigenetic processes associated with cellular adaptation to stressful conditions, and so it could be a direct consequence of stress-buffering mechanisms that allow cells with aberrant phenotypes (not necessarily associated with genetic mutations) to survive and propagate within the organism. We put forward the hypothesis that there would be an inverse correlation between the activation threshold of the cellular stress responses (CSRs) and the risk of cancer, so that species or individuals with low-threshold CSRs will display a higher incidence or risk of cancer.



中文翻译:


癌症是一种由细胞应激反应引起的疾病吗?



几十年来,体细胞突变理论(SMT)一直是癌症研究的主导范式,导致教科书认为癌症从根本上来说是一种遗传疾病。然而,最近的发现表明,包括“致癌”突变在内的突变在正常体细胞中广泛存在,这表明突变对于癌症的发生可能是必要的,但还不够充分。事实上,一个基本但尚未解答的问题是肿瘤发生的第一步是否对应于突变事件。另一方面,一段时间以来,人们已经认识到参与缓冲细胞应激的分子过程在癌症进展中的重要作用。然而,它们的作用被认为是假定的致癌突变的次要或补充作用。在这里,我们提出并讨论证据,表明癌症可能起源于与细胞适应压力条件相关的表观遗传过程,因此它可能是压力缓冲机制的直接结果,该机制允许细胞具有异常表型(不一定与基因突变相关)在生物体内生存和繁殖。我们提出假设,细胞应激反应(CSR)的激活阈值与癌症风险之间存在负相关,因此具有低CSR阈值的物种或个体将表现出较高的癌症发病率或风险。

更新日期:2021-05-25
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