The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream...The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling cascade.In addition,FOXM1 and FOXO3a also antagonize each other's activity by competitively binding to the same target genes,which are involved in chemotherapeutic drug sensitivity and resistance.Understanding the role and regulation of the FOXO-FOXM1 axis will provide insight into chemotherapeutic drug action and resistance in patients,and help to identify novel therapeutic approaches as well as diagnostic and predictive biomarkers.展开更多
The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance.Recent research shows that the forkhead transcription factor FOXM1 is a di...The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance.Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling pathway.Intriguingly,FOXM1 and FOXO3a also compete for binding to the same gene targets,which have a role in chemotherapeutic drug action and sensitivity.An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients,and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.展开更多
文摘The FOXO3a and FOXM1 forkhead transcription factors are key players in cancer initiation,progression,and drug resistance.Recent research shows that FOXM1 is a direct transcriptional target of FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling cascade.In addition,FOXM1 and FOXO3a also antagonize each other's activity by competitively binding to the same target genes,which are involved in chemotherapeutic drug sensitivity and resistance.Understanding the role and regulation of the FOXO-FOXM1 axis will provide insight into chemotherapeutic drug action and resistance in patients,and help to identify novel therapeutic approaches as well as diagnostic and predictive biomarkers.
基金sponsored by Breast Cancer Campaign,Cancer Research UK,Imperial College NHS Health Trust.
文摘The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance.Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a,a vital downstream effector of the PI3K-AKT-FOXO signaling pathway.Intriguingly,FOXM1 and FOXO3a also compete for binding to the same gene targets,which have a role in chemotherapeutic drug action and sensitivity.An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients,and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.
