Karakaidos Panagiotis, Verigos John, Magklara Angeliki
Institute of Molecular Biology and Biotechnology-Foundation for Research and Technology, Ioannina 45110, Greece.
Biomedical Research Foundation Academy of Athens, Athens 11527, Greece.
Cancers (Basel). 2019 Nov 20;11(12):1821. doi: 10.3390/cancers11121821.
A new exciting area in cancer research is the study of cancer stem cells (CSCs) and the translational implications for putative epigenetic therapies targeted against them. Accumulating evidence of the effects of epigenetic modulating agents has revealed their dramatic consequences on cellular reprogramming and, particularly, reversing cancer stemness characteristics, such as self-renewal and chemoresistance. Lysine specific demethylase 1 (LSD1/KDM1A) plays a well-established role in the normal hematopoietic and neuronal stem cells. Overexpression of LSD1 has been documented in a variety of cancers, where the enzyme is, usually, associated with the more aggressive types of the disease. Interestingly, recent studies have implicated LSD1 in the regulation of the pool of CSCs in different leukemias and solid tumors. However, the precise mechanisms that LSD1 uses to mediate its effects on cancer stemness are largely unknown. Herein, we review the literature on LSD1's role in normal and cancer stem cells, highlighting the analogies of its mode of action in the two biological settings. Given its potential as a pharmacological target, we, also, discuss current advances in the design of novel therapeutic regimes in cancer that incorporate LSD1 inhibitors, as well as their future perspectives.
癌症研究中一个令人兴奋的新领域是癌症干细胞（CSCs）的研究以及针对它们的潜在表观遗传疗法的转化意义。表观遗传调节剂作用的证据不断积累，揭示了它们对细胞重编程的显著影响，尤其是逆转癌症干性特征，如自我更新和化疗耐药性。赖氨酸特异性去甲基化酶1（LSD1/KDM1A）在正常造血干细胞和神经干细胞中发挥着既定作用。LSD1在多种癌症中均有过表达记录，在这些癌症中，该酶通常与更具侵袭性的疾病类型相关。有趣的是，最近的研究表明LSD1参与了不同白血病和实体瘤中癌症干细胞池的调控。然而，LSD1介导其对癌症干性影响的确切机制在很大程度上尚不清楚。在此，我们综述了关于LSD1在正常干细胞和癌症干细胞中作用的文献，突出了其在两种生物学环境中作用模式的相似性。鉴于其作为药物靶点的潜力，我们还讨论了在癌症中设计包含LSD1抑制剂的新型治疗方案的当前进展及其未来前景。
