School of Pharmaceutical Sciences, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001, PR China.
School of Pharmacy, Nantong University, Nantong 226001, PR China.
Biochem Pharmacol. 2024 Nov;229:116549. doi: 10.1016/j.bcp.2024.116549. Epub 2024 Sep 19.
As the first discovered histone demethylase, LSD1 plays a vital role in maintaining pathological processes such as cancer, infection, and immune diseases. Based on previous researches, LSD1 is highly expressed in sorts of tumor cells such as acute myeloid leukemia, non-small cell lung cancer, prostate cancer, breast cancer and gastric cancer, etc. Therefore, targeting LSD1 is a prospective strategy for tumor treatment. Cancer stem cells could preserve self-renewal, cell proliferation, cell migration and malignant phenotype. So, the reduction of tumor cell stemness can effectively inhibit the growth of tumor cells, which may be a new strategy for the treatment of cancers. Up to now, there exist many researches confirming the significant role of LSD1 in regulating the stemness characteristics such as embryonic stem cells differentiation. Many reports show that inhibition of LSD1 effectively decreases the property of cancer cell stemness. However, there lacks a detailed review about the relationship between LSD1 and cancer cell stemness. Herein, in this review, we summarized the mechanisms how LSD1 regulates cell stemness comprehensively. In addition, some related inhibitors targeting LSD1 to reduce the proliferation characteristics of cancer stem cells are also described.
作为首个被发现的组蛋白去甲基化酶，LSD1 在维持癌症、感染和自身免疫性疾病等病理过程中起着至关重要的作用。基于先前的研究，LSD1 在各种肿瘤细胞中高度表达，如急性髓系白血病、非小细胞肺癌、前列腺癌、乳腺癌和胃癌等。因此，靶向 LSD1 是肿瘤治疗的一种有前景的策略。肿瘤干细胞可以保持自我更新、细胞增殖、细胞迁移和恶性表型。因此，减少肿瘤细胞干性可以有效地抑制肿瘤细胞的生长，这可能是癌症治疗的一种新策略。到目前为止，有许多研究证实 LSD1 在调节干细胞特性（如胚胎干细胞分化）方面具有重要作用。许多报告表明，抑制 LSD1 能有效降低癌细胞干性。然而，目前缺乏关于 LSD1 与癌细胞干性之间关系的详细综述。因此，在这篇综述中，我们全面总结了 LSD1 调节细胞干性的机制。此外，还描述了一些针对 LSD1 的相关抑制剂，这些抑制剂可以减少癌症干细胞的增殖特性。
