title: BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10.
abstract: BRMS1L (breast cancer metastasis suppressor 1 like, BRMS1-like) is a component of Sin3A-histone deacetylase (HDAC) co-repressor complex that suppresses target gene transcription. Here we show that reduced BRMS1L in breast cancer tissues is associated with metastasis and poor patient survival. Functionally, BRMS1L inhibits breast cancer cells migration and invasion by inhibiting epithelial-mesenchymal transition. These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signalling, through HDAC1 recruitment and histone H3K9 deacetylation at the promoter. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-β-catenin signalling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNA interference-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, whereas ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signalling in breast cancer cells and acts as a breast cancer metastasis suppressor.
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Gong
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Qu
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Lv
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Bodu
authors.initials: B
authors.lastname: Liu
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Weige
authors.initials: W
authors.lastname: Tan
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Fengxi
authors.initials: F
authors.lastname: Su
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Herui
authors.initials: H
authors.lastname: Yao
authors.affiliation: 1] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Guangzhou 510120, China [2] Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
mesh_terms: D000328:Adult; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056284:Histone Deacetylase 1 / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D009368:Neoplasm Transplantation; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D060508:Wnt3 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C410024:BRMS1 protein, human; C121168:FZD10 protein, human; D051157:Frizzled Receptors; C542541:MIRN106 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C555507:WNT3 protein, human; D060508:Wnt3 Protein; D051176:beta Catenin; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1