Loss of breast cancer metastasis suppressor 1 promotes ovarian cancer cell metastasis by increasing chemokine receptor 4 expression

Sheng,Xiu-Jie; Zhou,Ying-Qun; Song,Qing-Yuan; Zhou,Dong-Mei; Liu,Qi-Cai

doi:10.3892/or.2011.1596

Loss of breast cancer metastasis suppressor 1 promotes ovarian cancer cell metastasis by increasing chemokine receptor 4 expression

Authors:
- Xiu-Jie Sheng
- Ying-Qun Zhou
- Qing-Yuan Song
- Dong-Mei Zhou
- Qi-Cai Liu
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Affiliations: Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical College, Guangzhou 510150, P.R. China
Published online on: December 19, 2011 https://doi.org/10.3892/or.2011.1596
Pages: 1011-1018

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Abstract

Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that differentially regulates the expression of multiple genes, leading to suppression of metastasis without affecting orthotopic tumor growth. It has been demonstrated that BRMS1 may be correlated with advanced ovarian cancer. The aim of this study was to investigate the mechanisms of BRMS1 involvement in ovarian cancer metastasis. We constructed a plasmid containing a short hairpin RNA (shRNA) against BRMS1 and transfected it into the ovarian cancer cell line OVCAR3. Real‑time reverse transcription polymerase chain reaction (real‑time PCR) and Western blot analyses demonstrated that BRMS1 expression was efficiently downregulated. Stable suppression of BRMS1 significantly enhanced cell adhesion, migration, invasion and angiogenesis. We also found that chemokine receptor 4 (CXCR4) was upregulated at both the mRNA and protein levels. When approaching for the mechanism, we discovered that activation of the nuclear factor‑κB (NF‑κB) signaling pathway mediated CXCR4 upregulation, as demonstrated by the electrophoretic mobility shift assay (EMSA). Collectively, these results suggest that attenuation of BRMS1 may play a critical role in promoting migration, invasion and angiogenesis of ovarian cancer cells and BRMS1 may regulate the metastatic potential at least in part through upregulation of CXCR4 via NF‑κB activation. Restoration of BRMS1 function is thus a potential new strategy for treating human ovarian cancer.

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