Martinez Anne-Marie
IGH, Univ Montpellier, CNRS, Montpellier, France.
Adv Exp Med Biol. 2025;1482:155-179. doi: 10.1007/978-3-031-97035-1_9.
This chapter investigates the role of epigenetic regulation in tumorigenesis using Drosophila melanogaster as a model organism. It underscores the advantages of Drosophila for studying epigenetic mechanisms in cancer and focuses on key epigenetic regulators, such as Polycomb and Trithorax complexes, which modulate chromatin structure and gene expression. The chapter explores the roles of these complexes in various Drosophila tissues, including imaginal discs, the central nervous system, and adult stem cells, emphasizing their context-dependent functions in both tumor suppression and promotion. It challenges the somatic mutation theory (SMT) of cancer by emphasizing theories and experimental results suggesting a major contribution of epigenetic mechanisms in cancer initiation and progression. The concept of tumor reversion through epigenetic reprogramming is introduced, suggesting that non-mutational changes can revert tumor cells to a benign state. The tissue organization field theory (TOFT) and the epigenetic progenitor hypothesis are discussed to explain the epigenetic origins of cancer. Significant data highlight the critical role of epigenetic regulation in maintaining cellular identity, preventing tumorigenesis, and contributing to cancer when dysregulated. The chapter discusses the potential for epigenetic therapies and the need for further research to unravel the complex interplay between genetic and epigenetic factors in cancer.
本章以黑腹果蝇作为模式生物，研究表观遗传调控在肿瘤发生中的作用。它强调了果蝇在研究癌症表观遗传机制方面的优势，并聚焦于关键的表观遗传调节因子，如多梳蛋白和三胸复合物，它们可调节染色质结构和基因表达。本章探讨了这些复合物在果蝇的各种组织中的作用，包括成虫盘、中枢神经系统和成年干细胞，强调了它们在肿瘤抑制和促进中的背景依赖性功能。通过强调表明表观遗传机制在癌症起始和进展中起主要作用的理论和实验结果，本章对癌症的体细胞突变理论（SMT）提出了挑战。引入了通过表观遗传重编程实现肿瘤逆转的概念，表明非突变变化可使肿瘤细胞恢复到良性状态。讨论了组织组织场理论（TOFT）和表观遗传祖细胞假说，以解释癌症的表观遗传起源。大量数据突出了表观遗传调控在维持细胞身份、预防肿瘤发生以及失调时促进癌症方面的关键作用。本章讨论了表观遗传疗法的潜力以及进一步研究以揭示癌症中遗传和表观遗传因素之间复杂相互作用的必要性。
