Details

Autor(en) / Beteiligte

• Xu, Zhiyao
• Zhou, Zhuha
• Zhang, Jing
• Xuan, Feichao
• Fan, Mengjing
• Zhou, Difan
• Liuyang, Zhenyu
• Ma, Ximei
• Hong, Yiyang
• Wang, Yihong
• Sharma, Sherven
• Dong, Qinghua
• Wang, Guanyu

Titel

Targeting BMI-1-mediated epithelial–mesenchymal transition to inhibit colorectal cancer liver metastasis

Ist Teil von

• Acta pharmaceutica Sinica. B, 2021-05, Vol.11 (5), p.1274-1285

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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-3β 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.