凋亡与多倍体在发育和癌症中的拮抗关系。
The antagonistic relationship between apoptosis and polyploidy in development and cancer.
机构信息
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
出版信息
Semin Cell Dev Biol. 2024 Mar 15;156:35-43. doi: 10.1016/j.semcdb.2023.05.009. Epub 2023 Jun 16.
One of the important functions of regulated cell death is to prevent cells from inappropriately acquiring extra copies of their genome, a state known as polyploidy. Apoptosis is the primary cell death mechanism that prevents polyploidy, and defects in this apoptotic response can result in polyploid cells whose subsequent error-prone chromosome segregation are a major contributor to genome instability and cancer progression. Conversely, some cells actively repress apoptosis to become polyploid as part of normal development or regeneration. Thus, although apoptosis prevents polyploidy, the polyploid state can actively repress apoptosis. In this review, we discuss progress in understanding the antagonistic relationship between apoptosis and polyploidy in development and cancer. Despite recent advances, a key conclusion is that much remains unknown about the mechanisms that link apoptosis to polyploid cell cycles. We suggest that drawing parallels between the regulation of apoptosis in development and cancer could help to fill this knowledge gap and lead to more effective therapies.
细胞程序性死亡的一个重要功能是防止细胞不恰当地获得额外的基因组拷贝，这种状态被称为多倍体。细胞凋亡是防止多倍体形成的主要细胞死亡机制，而这种凋亡反应的缺陷可能导致多倍体细胞，其随后易错的染色体分离是基因组不稳定性和癌症进展的主要原因。相反，一些细胞主动抑制细胞凋亡以成为多倍体，这是正常发育或再生的一部分。因此，尽管细胞凋亡可以防止多倍体的形成，但多倍体状态也可以主动抑制细胞凋亡。在这篇综述中，我们讨论了在发育和癌症中理解细胞凋亡和多倍体之间拮抗关系的进展。尽管最近取得了一些进展，但一个关键的结论是，关于将细胞凋亡与多倍体细胞周期联系起来的机制，我们仍然知之甚少。我们认为，在发育和癌症中细胞凋亡的调控之间进行类比，可能有助于填补这一知识空白，并导致更有效的治疗方法。
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