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Targeting BMI-1-mediated epithelial-mesenchymal transition to inhibit colorectal cancer liver metastasis.
- Source :
-
Acta pharmaceutica Sinica. B [Acta Pharm Sin B] 2021 May; Vol. 11 (5), pp. 1274-1285. Date of Electronic Publication: 2020 Nov 28. - Publication Year :
- 2021
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Abstract
- 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 upregulating snail via AKT/GSK-3 β pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, 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.<br />Competing Interests: The authors declare no conflicts of interest.<br /> (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)
Details
- Language :
- English
- ISSN :
- 2211-3835
- Volume :
- 11
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Acta pharmaceutica Sinica. B
- Publication Type :
- Academic Journal
- Accession number :
- 34094833
- Full Text :
- https://doi.org/10.1016/j.apsb.2020.11.018