PDF(Pubmed)
Abstract：
Pancreatic cancer is a malignancy arising from the endocrine or exocrine compartment of this organ. Tumors from exocrine origin comprise over 90% of all pancreatic cancers diagnosed. Of these, pancreatic ductal adenocarcinoma (PDAC) is the most common histological subtype. The five-year survival rate for PDAC ranged between 5 and 9% for over four decades, and only recently saw a modest increase to ∼12-13%, making this a severe and lethal disease. Like other cancers, PDAC initiation stems from genetic changes. However, therapeutic targeting of PDAC genetic drivers has remained relatively unsuccessful, thus the focus in recent years has expanded to the non-genetic factors underlying the disease pathogenesis. Specifically, it has been proposed that dynamic changes in the epigenetic landscape promote tumor growth and metastasis. Emphasis has been given to the re-organization of enhancers, essential regulatory elements controlling oncogenic gene expression, commonly marked my histone 3 lysine 4 monomethylation (H3K4me1). H3K4me1 is typically deposited by histone lysine methyltransferases (KMTs). While well characterized as oncogenes in other cancer types, recent work has expanded the role of KMTs as tumor suppressor in pancreatic cancer. Here, we review the role and translational significance for PDAC development and therapeutics of KMTs.
摘要：
胰腺癌是由该器官的内分泌或外分泌室引起的恶性肿瘤。来自外分泌来源的肿瘤占所有诊断的胰腺癌的90%以上。其中,胰腺导管腺癌（PDAC）是最常见的组织学亚型。在过去的四十年中，PDAC的五年生存率在5％至9％之间。直到最近才出现小幅增长，达到12%-13%，使这成为一种严重而致命的疾病。像其他癌症一样，PDAC起始源于遗传变化。然而,PDAC遗传驱动因素的治疗靶向仍然相对不成功，因此，近年来的焦点已扩展到疾病发病机理的非遗传因素。具体来说,已经提出表观遗传景观的动态变化促进肿瘤的生长和转移。强调了增强剂的重组，控制致癌基因表达的必需调控元件，通常标记为我的组蛋白3赖氨酸4单甲基化(H3K4me1)。H3K4me1通常由组蛋白赖氨酸甲基转移酶(KMTs)沉积。虽然在其他癌症类型中被很好地描述为癌基因，最近的工作扩大了KMT在胰腺癌中作为肿瘤抑制因子的作用。这里,我们综述了KMTs在PDAC开发和治疗中的作用和翻译意义。
