Wu Kou-Juey
Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Chang Gung Med J. 2011 May-Jun;34(3):229-38.
Cancer stemness is a concept used to describe a minor population of cells (cancer stem cells-CSCs) residing in a tumor, which possess self-renewal properties and are resistant to chemo/radiation therapy. Epithelial-mesenchymal transition (EMT), a major mechanism of cancer metastasis, is a process which generates cells with stem-like properties. The relationship between cancer stemness and EMT is well documented but without detailed mechanistic explanation. Bmi1 belongs to the polycomb repressive complex 1 (PRC1) which maintains self-renewal and stemness. Recent results showed that Twist1, an EMT regulator, directly activates Bmi1 and these two molecules function together to mediate cancer stemness and EMT. These results provide a molecular explanation of the relationship between cancer stemness and EMT. Bmi1 is frequently overexpressed in various types of human cancers and can confer drug resistance. Twist1 is also overexpressed in various human cancers with prognostic significance. The functional interdependence between Twist1 and Bmi1 provides a fresh insight into the molecular mechanism of EMT-induced cancer stemness. Further investigation of the mechanisms mediating EMT and cancer stemness will be helpful in the management and treatment of metastatic cancers.
癌症干性是一个用于描述存在于肿瘤中的一小部分细胞（癌症干细胞，CSCs）的概念，这些细胞具有自我更新特性，并且对化疗/放疗具有抗性。上皮-间质转化（EMT）是癌症转移的主要机制，是一个产生具有干细胞样特性细胞的过程。癌症干性与EMT之间的关系已有充分记载，但缺乏详细的机制解释。Bmi1属于维持自我更新和干性的多梳抑制复合物1（PRC1）。最近的结果表明，EMT调节因子Twist1直接激活Bmi1，这两个分子共同作用以介导癌症干性和EMT。这些结果为癌症干性与EMT之间的关系提供了分子解释。Bmi1在各种类型的人类癌症中经常过度表达，并可赋予耐药性。Twist1在各种人类癌症中也过度表达，具有预后意义。Twist1和Bmi1之间的功能相互依赖为EMT诱导的癌症干性的分子机制提供了新的见解。进一步研究介导EMT和癌症干性的机制将有助于转移性癌症的管理和治疗。
