title: Direct activation of Bmi1 by Twist1: implications in cancer stemness, epithelial-mesenchymal transition, and clinical significance.
abstract: 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.
authors: Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan. kjwu2@ym.edu.tw
authors: Kou-Juey
authors: KJ
authors: Wu
mesh_terms: D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D009369:Neoplasms / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009687:Nuclear Proteins / Q000502:physiology*; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000502:physiology*
chemical_list: C069077:BMI1 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D063150:Polycomb Repressive Complex 1