Department of Surgery, University of Michigan, Ann Arbor, MI, United States.
Department of Surgery, University of Michigan, Ann Arbor, MI, United States; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, United States.
Semin Cancer Biol. 2019 Aug;57:19-26. doi: 10.1016/j.semcancer.2018.09.008. Epub 2018 Sep 28.
Pancreatic Cancer (PDA) is an aggressive malignancy characterized by early spread and a high mortality. Current studies suggest that a subpopulation of cells exist within tumors, cancer stem cell (CSC), which are capable of self-renewal and give rise to unique progeny which form the major neoplastic cellular component of tumors. While CSCs constitute a small cellular subpopulation within the tumor, their resistance to chemotherapy and radiation make them an important therapeutic target for eradication. Along with distinctive phenotypic properties, CSCs possess a unique metabolic plasticity allowing them to rapidly respond and adapt to environmental changes. These cells and their progeny also display a significantly altered epigenetic state with distinctive patterns of DNA methylation. Several mechanisms of cross-talk between epigenetic and metabolic pathways in PDA exist which ultimately contribute to the observed cellular plasticity and enhanced tumorigenesis. In this review we discuss various examples of this metabolic-epigenetic interplay and how it may constitute a new avenue for therapy specifically targeting CSCs in PDA.
胰腺癌（PDA）是一种侵袭性恶性肿瘤，其特征为早期扩散和高死亡率。目前的研究表明，肿瘤内存在一小部分细胞，即癌症干细胞（CSC），它们具有自我更新的能力，并产生独特的后代，形成肿瘤的主要肿瘤细胞成分。虽然 CSC 构成了肿瘤中的一小部分细胞亚群，但它们对化疗和放疗的耐药性使它们成为消除肿瘤的重要治疗靶点。除了独特的表型特性外，CSC 还具有独特的代谢可塑性，使其能够快速响应和适应环境变化。这些细胞及其后代还表现出明显改变的表观遗传状态，具有独特的 DNA 甲基化模式。PDA 中存在几种表观遗传和代谢途径之间相互作用的机制，这些机制最终导致观察到的细胞可塑性和增强的肿瘤发生。在这篇综述中，我们讨论了这种代谢-表观遗传相互作用的各种例子，以及它如何可能构成针对 PDA 中的 CSC 的治疗的新途径。
