Laboratoire de Biochimie, EA3922, UFR-ST, Université de Franche-Comté, 25035 Besançon Cedex, France.
Centre de Recherche en Cancérologie Nantes-Angers, INSERM, U892, Equipe Apoptose et progression tumorale, Equipe labellisée Ligue Nationale Contre le Cancer, 44007 Nantes, France.
Cells. 2013 Jul 18;2(3):545-73. doi: 10.3390/cells2030545.
Apoptosis is a cell death programme primordial to cellular homeostasis efficiency. This normal cell suicide program is the result of the activation of a cascade of events in response to death stimuli. Apoptosis occurs in normal cells to maintain a balance between cell proliferation and cell death. A deregulation of this balance due to modifications in the apoptosic pathway leads to different human diseases including cancers. Apoptosis resistance is one of the most important hallmarks of cancer and some new therapeutical strategies focus on inducing cell death in cancer cells. Nevertheless, cancer cells are resistant to treatment inducing cell death because of different mechanisms, such as DNA mutations in gene coding for pro-apoptotic proteins, increased expression of anti-apoptotic proteins and/or pro-survival signals, or pro-apoptic gene silencing mediated by DNA hypermethylation. In this context, aberrant DNA methylation patterns, hypermethylation and hypomethylation of gene coding for proteins implicated in apoptotic pathways are possible causes of cancer cell resistance. This review highlights the role of DNA methylation of apoptosis-related genes in cancer cell resistance.
细胞凋亡是细胞内稳态效率所必需的细胞死亡程序。这种正常的细胞自杀程序是对死亡刺激的一系列事件的激活的结果。凋亡发生在正常细胞中，以维持细胞增殖和细胞死亡之间的平衡。由于凋亡途径的改变，这种平衡的失调导致了包括癌症在内的不同人类疾病。凋亡抵抗是癌症的最重要特征之一，一些新的治疗策略集中在诱导癌细胞死亡上。然而，由于不同的机制，如编码促凋亡蛋白的基因中的 DNA 突变、抗凋亡蛋白和/或生存信号的表达增加，或由 DNA 高甲基化介导的促凋亡基因沉默，癌细胞对诱导细胞死亡的治疗具有抵抗力。在这种情况下，凋亡相关基因的异常 DNA 甲基化模式、编码凋亡途径蛋白的基因的高甲基化和低甲基化可能是癌细胞耐药的原因。本综述强调了凋亡相关基因的 DNA 甲基化在癌细胞耐药中的作用。
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