Direct Activation of Bmi1 by Twist1: Implications in Cancer Stemness, Epithelial-Mesenchymal Transition, and Clinical Significance

Cancer stemness is a concept used to describe a minorpopulation of cells (cancer stem cells-CSCs) residing in atumor, which possess self-renewal properties and are resistantto chemo/radiation therapy. Epithelial-mesenchymal transition(EMT), a major mechanism of cancer metastasis, is a processwhich generates cells with stem-like properties. The relationship between cancer stemness and EMT is well documentedbut without detailed mechanistic explanation. Bmi1 belongs tothe polycomb repressive complex 1 (PRC1) which maintainsself-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 frequentlyoverexpressed in various types of human cancers and can confer drug resistance. Twist1 is also overexpressed in various human cancers with prognosticsignificance. The functional interdependence between Twist1 and Bmi1 provides a freshinsight 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