Department of Pathology, Yale School of Medicine, New Haven, CT, U.S.A.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, U.S.A.
Biochem J. 2021 Sep 17;478(17):3373-3393. doi: 10.1042/BCJ20210084.
Cancer metastasis remains a major clinical challenge for cancer treatment. It is therefore crucial to understand how cancer cells establish and maintain their metastatic traits. However, metastasis-specific genetic mutations have not been identified in most exome or genome sequencing studies. Emerging evidence suggests that key steps of metastasis are controlled by reversible epigenetic mechanisms, which can be targeted to prevent and treat the metastatic disease. A variety of epigenetic mechanisms were identified to regulate metastasis, including the well-studied DNA methylation and histone modifications. In the past few years, large scale chromatin structure alterations including reprogramming of the enhancers and chromatin accessibility to the transcription factors were shown to be potential driving force of cancer metastasis. To dissect the molecular mechanisms and functional output of these epigenetic changes, it is critical to use advanced techniques and alternative animal models for interdisciplinary and translational research on this topic. Here we summarize our current understanding of epigenetic aberrations in cancer progression and metastasis, and their implications in developing new effective metastasis-specific therapies.
癌症转移仍然是癌症治疗的主要临床挑战。因此，了解癌细胞如何建立和维持其转移特性至关重要。然而，在大多数外显子组或基因组测序研究中尚未发现转移特异性的基因突变。新出现的证据表明，转移的关键步骤受可逆的表观遗传机制控制，可靶向这些机制来预防和治疗转移性疾病。已确定多种表观遗传机制来调节转移，包括研究充分的 DNA 甲基化和组蛋白修饰。在过去的几年中，大规模染色质结构改变，包括增强子的重编程和转录因子对染色质可及性，被显示为癌症转移的潜在驱动力。为了剖析这些表观遗传变化的分子机制和功能结果，使用先进的技术和替代的动物模型来进行该主题的跨学科和转化研究至关重要。在这里，我们总结了我们目前对癌症进展和转移中的表观遗传异常及其在开发新的有效的转移性特异性治疗方法中的意义的理解。
