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.

中文翻译：

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表观遗传学在癌症进展和转移中的作用

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征至关重要。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基因突变。新出现的证据表明，转移的关键步骤由可逆的表观遗传机制控制，可以针对预防和治疗转移性疾病。确定了多种表观遗传机制来调节转移，包括充分研究的 DNA 甲基化和组蛋白修饰。在过去几年中，包括增强子重编程和染色质对转录因子的可及性在内的大规模染色质结构改变被证明是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输出，使用先进技术和替代动物模型对该主题进行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的理解，以及它们在开发新的有效转移特异性疗法中的意义。