【摘 要】
:
Liver is the most common metastatic site for colorectal cancer(CRC),there is no satisfied approach to treat CRC liver metastasis(CRCLM).Here,we investigated the role of a polycomb protein BMI-1 in CRCLM.Immunohistochemical analysis showed that BMI-1 expre
【机 构】
:
Biomedical Research Center,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou
论文部分内容阅读
Liver is the most common metastatic site for colorectal cancer(CRC),there is no satisfied approach to treat CRC liver metastasis(CRCLM).Here,we investigated the role of a polycomb protein BMI-1 in CRCLM.Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage,invasion depth and right-sided primary tumor.Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition(EMT),while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT.The effects of BMI-1 in CRC cells were related to upregulat-ing snail via AKT/GSK-3β pathway.Furthermore,knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model.Meanwhile,BMI-1 overexpression in Ls174Tand DLD1 significantly increased CRCLM.Moreover,sodium butyrate,a histone deacetylase and BMI-1 inhib-itor,reduced HCT116 and LOVO liver metastasis in immunodeficient mice.Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.
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