Bmi-1 is a member of the Polycomb repressor complex 1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells.Despite three decades of ...Bmi-1 is a member of the Polycomb repressor complex 1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells.Despite three decades of research that have elucidated the transcriptional regulation,post-translational modifications and functions of Bmi-1 in regulating the DNA damage response,cellular bioenergetics,and pathologies,the entire potential of a protein with such varied functions remains to be realized.This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer.Additionally,since cancer stem cells are emerging as a new paradigm for therapy resistance,the role of Bmi-1 in this perspective is also highlighted.The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy.Nonetheless,new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target.展开更多
Resistance to chemotherapy is a prominent clinical problem in high grade serous ovarian cancer(HGSOC).1 An inadequate understanding of adaptive signaling coupled with limited treatment options for a chemoresistant tum...Resistance to chemotherapy is a prominent clinical problem in high grade serous ovarian cancer(HGSOC).1 An inadequate understanding of adaptive signaling coupled with limited treatment options for a chemoresistant tumor are likely causes for poor outcomes.We previously reported that BMI1,a stem-cell factor is instrumental in regulating chemoresistance.2,3 However,to advance anti-BMI1 therapy from the bench to the bedside,efficacy needs to be tested in patient-derived chemoresistant HGSOC models,which is lacking.展开更多
基金This study was supported by the National Institutes of Health(NIH)CA157481 awarded to RB.
文摘Bmi-1 is a member of the Polycomb repressor complex 1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells.Despite three decades of research that have elucidated the transcriptional regulation,post-translational modifications and functions of Bmi-1 in regulating the DNA damage response,cellular bioenergetics,and pathologies,the entire potential of a protein with such varied functions remains to be realized.This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer.Additionally,since cancer stem cells are emerging as a new paradigm for therapy resistance,the role of Bmi-1 in this perspective is also highlighted.The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy.Nonetheless,new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target.
基金This study was supported by research awards from the US Department of Defense to RB(No.W81XWH1810073,and W81XWH1810054)Histology and immunohistochemistry service was provided by the Stephenson Cancer Tissue Pathology research core supported by the NIGMS Grant P20GM103639 and NCI Grant P30CA225520 of the NIH.
文摘Resistance to chemotherapy is a prominent clinical problem in high grade serous ovarian cancer(HGSOC).1 An inadequate understanding of adaptive signaling coupled with limited treatment options for a chemoresistant tumor are likely causes for poor outcomes.We previously reported that BMI1,a stem-cell factor is instrumental in regulating chemoresistance.2,3 However,to advance anti-BMI1 therapy from the bench to the bedside,efficacy needs to be tested in patient-derived chemoresistant HGSOC models,which is lacking.
