Khaled Noura, Bidet Yannick
Laboratoire d'Oncologie Moléculaire, Centre Jean PERRIN et IMoST, UMR 1240, Inserm/Université Clermont Auvergne 58 rue Montalembert, 63000 Clermont-Ferrand, France.
Cancers (Basel). 2019 Apr 18;11(4):559. doi: 10.3390/cancers11040559.
Breast cancer is the most common cancer and leading cause of cancer death among women worldwide, encompassing a wide heterogeneity of subtypes with different clinical features. During the last two decades, the use of targeted therapies has emerged in clinical research in order to increase treatment efficiency, improve prognosis and reduce recurrence. However, the triple negative breast cancer (TNBC) subtype remains a clinical challenge, with poor prognosis since no therapeutic targets have been identified. This aggressive breast cancer entity lacks expression of oestrogen receptor (ER) and progesterone receptor (PR), and it does not overexpress human epidermal growth factor receptor 2 (HER2). The major reason for TNBC poor prognosis is early therapeutic escape from conventional treatments, leading to aggressive metastatic relapse. Metastases occur after an epithelial-mesenchymal transition EMT of epithelial cells, allowing them to break free from the primary tumour site and to colonize distant organs. Cancer-associated EMT consists not only of acquired migration and invasion ability, but involves complex and comprehensive reprogramming, including changes in metabolism, expression levels and epigenetic. Recently, many studies have considered epigenetic alterations as the primary initiator of cancer development and metastasis. This review builds a picture of the epigenetic modifications implicated in the EMT of breast cancer. It focuses on TNBC and allows comparisons with other subtypes. It emphasizes the role of the main epigenetic modifications lncRNAs, miRNAs, histone and DNA- modifications in tumour invasion and appearance of metastases. These epigenetic alterations can be considered biomarkers representing potential diagnostic and prognostic factors in order to define a global metastatic signature for TNBC.
乳腺癌是全球女性中最常见的癌症及癌症死亡的主要原因，包含具有不同临床特征的多种异质性亚型。在过去二十年中，为了提高治疗效率、改善预后并减少复发，靶向治疗已在临床研究中出现。然而，三阴性乳腺癌（TNBC）亚型仍然是一个临床挑战，由于尚未确定治疗靶点，其预后较差。这种侵袭性乳腺癌实体缺乏雌激素受体（ER）和孕激素受体（PR）的表达，且不高表达人表皮生长因子受体2（HER2）。TNBC预后不良的主要原因是早期从传统治疗中逃逸，导致侵袭性转移复发。转移发生在上皮细胞经历上皮-间质转化（EMT）之后，使它们能够从原发肿瘤部位脱离并在远处器官定植。癌症相关的EMT不仅包括获得的迁移和侵袭能力，还涉及复杂而全面的重编程，包括代谢、表达水平和表观遗传的变化。最近，许多研究将表观遗传改变视为癌症发展和转移的主要启动因素。本综述描绘了与乳腺癌EMT相关的表观遗传修饰情况。它聚焦于TNBC，并与其他亚型进行比较。它强调了主要表观遗传修饰长链非编码RNA（lncRNAs）、微小RNA（miRNAs）、组蛋白和DNA修饰在肿瘤侵袭和转移出现中的作用。这些表观遗传改变可被视为代表潜在诊断和预后因素的生物标志物，以便为TNBC定义一个全局转移特征。
