Sun Yat-Sen University,China
Dr. Chang Gong has completed her MD in 2004 and PhD in 2010 from Sun Yat-Sen University as well as postdoctoral studies from INSERM, France. She is an associate professor of breast surgery in Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University. She focuses on the mechanisms of drug resistance and metastasis of breast cancer. She has published 15 papers in reputed journals.
BRMS1L (breast cancer metastasis suppressor 1 like，BRMS1-like) is a component of the SIN3A-HDAC corepressor complex that suppresses target gene transcription. However, the contribution of BRMS1L in cancer development is not well characterized. Here, we show that reduced BRMS1L in breast cancer tissues is associated with tumor metastasis and poor patient survival. Functionally, BRMS1L inhibits migration and invasion of breast cancer cells by inhibiting epithelial-mesenchymal transition (EMT). These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signaling, by facilitating the recruitment of HDAC1 to its promoter and enhancing histone H3K9 deacetylation. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10--catenin signaling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction, which is responsible for Wnt pathway activation and the ensuing EMT in breast cancer cells. RNAi-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, while ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signaling in breast cancer cells and acts as a breast cancer metastasis suppressor.
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