Department of Occupational Medicine, Far Eastern Memorial Hospital, New Taipei City, Taipei, Taiwan.
Clin Exp Pharmacol Physiol. 2012 Aug;39(8):668-73. doi: 10.1111/j.1440-1681.2011.05594.x.
Cancer metastasis is the major cause of cancer-related death despite significant improvements in multimodal cancer therapy. Epithelial-mesenchymal transition (EMT), a major mechanism of cancer metastasis, is a process that generates cells with stem cell-like properties (cancer stemness). Cancer stemness is a concept that describes a minor population of cells (cancer stem cells) residing within a tumour that are able to self-renew and are resistant to conventional therapy. The mechanisms delineating the generation of cancer stemness and its connection to cancer metastasis remain largely unknown. Twist1 is an EMT regulator and increased Twist1 expression, which has prognostic significance in various human cancers, has been widely reported. Bmi1 is a critical component of polycomb repressive complex (PRC) 1, which maintains self-renewal and stemness. Bmi1 is frequently overexpressed in different types of human cancers and can induce drug resistance (Table 2). Recent studies have shown that Twist1 directly activates Bmi1 expression and that these two molecules function together to mediate cancer stemness and EMT. These results present a unique mechanism of EMT-induced cancer metastasis and stemness. Further investigation of the mechanisms of EMT-mediated cancer metastasis and stemness will contribute to the management and treatment of metastatic cancers.
癌症转移是癌症相关死亡的主要原因，尽管癌症的多模式治疗有了显著的进步。上皮-间充质转化（EMT）是癌症转移的主要机制之一，它是一个产生具有干细胞样特性的细胞的过程（癌症干性）。癌症干性是一个描述肿瘤内存在的一小部分细胞（癌症干细胞）的概念，这些细胞能够自我更新，并对传统治疗具有抗性。阐明癌症干性的产生及其与癌症转移的关系的机制在很大程度上仍然未知。Twist1 是 EMT 的调节剂，Twist1 表达的增加在各种人类癌症中具有预后意义，这已被广泛报道。Bmi1 是多梳抑制复合物（PRC）1 的关键组成部分，它维持自我更新和干性。Bmi1 在不同类型的人类癌症中经常过表达，并能诱导耐药（表 2）。最近的研究表明，Twist1 直接激活 Bmi1 的表达，这两个分子共同作用介导癌症干性和 EMT。这些结果提出了 EMT 诱导的癌症转移和干性的独特机制。进一步研究 EMT 介导的癌症转移和干性的机制将有助于转移性癌症的管理和治疗。
