Atlas of Genetics and Cytogenetics in Oncology and Haematology

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BRMS1 (breast cancer metastasis suppressor 1)

Written2008-12Yvonne Buggy, Michael J Duffy
Drug Safety Research Unit, Southampton, UK (YB); UCD School of Medicine, Medical Science, Conway Institute, University College Dublin, St. Vincent's University Hospital, Dublin, Ireland (MJD)

(Note : for Links provided by Atlas : click)


Alias (NCBI)DKFZP564A063
HGNC Alias symbDKFZP564A063
HGNC Previous namebreast cancer metastasis suppressor 1
LocusID (NCBI) 25855
Atlas_Id 841
Location 11q13.2  [Link to chromosome band 11q13]
Location_base_pair Starts at 66337339 and ends at 66345104 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping BRMS1.png]
Local_order Chr 11: 65861380 - 65869158 (minus strand)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)


  Exon-Intron structure of human BRMS1.
Description BRMS1 is a functioning gene comprising 10 exons and spanning 7.8 kb of genomic DNA. Alternative splicing results in two mRNA transcripts, translating into two distinct proteins, 246 amino acids and 290 amino acids in length, respectively (Seraj et al., 2000). The longer transcript uses an alternative splice site in the 3' untranslated terminal exon which results in the use of a downstream stop codon. The encoded protein has a longer distinct C-terminus.
Transcription Structural analysis of the BRMS1 promoter has revealed the presence of two hypermethylated cytosine-phosphoguanine (CpG) islands (Metge et al., 2008). Hypermethylation of CpG islands restricts the activity of the BRMS1 protein, mainly due the tightly packed nucleosomes (Metge et al., 2008). Gene expression can also be suppressed by blocking transcription factor binding.


Note 1-246 amino acids
Coiled-Coil Motifs: 51-81 and 147-180 amino acids
Imperfect Leucine Zippers: 67-88, 131-152, 138-159, 153-174 and 160-181 amino acids
Nuclear Localisation Signals: 198-205, 239-245 amino acids
cAMP/cGMP Phosphorylation Sites: 55-58 and 240-243 amino acids
  Schematic representation of the BRMS1 protein. The coiled coil motifs are shown in yellow, nuclear localisation signals are shown in blue, the imperfect leucine zipper motifs are shown in green and the cAMP/cGMP phosphorylation sites are shown in purple.
Description The BRMS1 protein consists of 246 amino acids, two coiled-coil motifs and a number of imperfect leucine zipper motifs at amino acids 67-88, 131-152, 138-159, 153-174 and 160-181, respectively. Several putative phosphorylation sites have also been identified (see diagram above) (Seraj et al., 2000). The full length protein is 2.8 kDa. In addition, a novel BRMS1-homologue protein (p40) has been identified, which may play a role in transcription repression by recruiting histone deacetylase complexes (Nikolaev et al., 2004).
Expression BRMS1 was originally identified by differential display analysis. Transfection of BRMS1 cDNA into MDA-MB-435 and MDA-MB-231 breast cancer cell lines was shown to suppress formation of metastasis without affecting tumourigenicity (Samantet al., 2000). BRMS1 overexpression also inhibits lung and lymph node metastasis in experimental melanoma and ovarian cancer models (Shevde et al., 2002; Zhang et al., 2006). Reduced expression of BRMS1 has been correlated with poor prognosis in human breast cancer (Zhang et al., 2006). In addition, reduced expression of BRMS1 has been observed in breast cancer brain metastasis (Stark et al., 2005).
Localisation The BRMS1 protein is predominantly located in the nucleus.
Function Breast cancer metastasis suppressor gene 1 is a member of a growing family of metastasis suppressor genes which prevent the development of metastasis without affecting tumour growth (Welch et al., 2000). The main cause of mortality in cancer patients is the formation of metastasis, a multistep process, modulated largely by activators and suppressors of metastasis (Chambers et al., 2002; Duffy, 1996). BRMS1 has been shown to suppress metastasis of human breast cancer and melanoma cells in nude mice (Seraj et al., 2000; Samant et al., 2000; Samant et al., 2002). It maps to chromosome 11, a region of the genome which has been implicated in the progression and metastasis of human breast cancer (Seraj et al., 2000).
Recent studies suggest that BRMS1 inhibits metastasis through an interaction with histone deacetylase complexes, resulting in aberrant gene regulation (Hurst et al., 2006; Samant et al., 2007). It is a selective component of the mSin3a/histone deacetylase corepressor complex and when activated results in basal transcriptional repression (Meehan et al., 2004). In addition, BRMS1 has been shown to negatively regulate activity, which is constitutively activated in many human cancers and plays an important role in apoptosis (Samant et al., 2007).
Metge et al. (2008) recently identified two hypermethylated CpG islands in the BRMS1 promoter . This group also observed reduced expression of BRMS1 in metastatic breast cancer cell lines. They hypothesized that promoter hypermethylation may be involved in this downregulation of BRMS1 expression (Metge et al., 2008). Methylation appears to be an important early event in the etiology of human breast cancer, resulting in the silencing of many tumour suppressor genes, including BRMS1 (Nephew et al., 2003). Metge et al. (2008) suggest that epigenetic silencing of BRMS1 may be an important prognostic indicator in human breast cancer .
Other functions of BRMS1 include restoring homotypic gap junctional intercellular communications (Samant et al., 2000; Shevde et al., 2002; Saunders et al., 2001), inhibiting expression of the metastasis-promoting chemokine osteopontin (Samant et al., 2007; DeWald et al., 2005). Furthermore, BRMS1 has been shown to play a role in phosphoinositide signaling.

Implicated in

Note A growing number of human malignancies (breast, ovarian, melanoma) have been associated with a decrease in BRMS1 expression, leading to an increased risk of metastasis and a decreased overall disease-free survival and poor prognosis (Shevde et al., 2002; Zhang et al., 2006; DeWald et al., 2005; Kelly et al., 2005).
Entity Breast cancer
Disease Overexpression of BRMS1 has been shown to reduce the metastatic ability of human breast cancer cells injected into nude mice (Seraj et al., 2000; Samant et al., 2006). Loss of BRMS1 protein expression correlated with reduced disease-free survival in human breast cancer and also with estrogen and progesterone receptor negative and HER-2/neu positive tumours, suggesting that BRMS1 plays a role in the biology of these tumours (Hicks et al., 2006). However, Kelly et al. (2005) showed expression of BRMS1 mRNA was independent of metastasis to lymph nodes, hormone receptor status and tumour size in human breast cancer . These conflicting findings suggest further investigations are necessary to elucidate the role of BRMS1 in the metastatic cascade.
Recently, Cicek et al. (2005) showed an inverse correlation between expression of BRMS1 and urokinase plasminogen activator (uPA) in metastatic breast cancer cell lines. The expression of uPA has long been associated with metastasis (Duffy et al., 1990). uPA catalyses the conversion of inactive plasminogen to plasmin, a broad spectrum protease, capable of catalyzing the degradation of most proteases in the extracellular matrix (Duffy et al., 1984). uPA was the first proteolytic enzyme shown to be associated with poor prognosis in breast cancer. In 1988, Duffy et al. showed that breast cancer patients with high levels of uPA had a significantly shorter disease-free survival compared with patients whose tumours expressed low levels of the enzyme. uPA is currently one of the best validated prognostic marker for breast cancer (Look et al., 2002; Nijziel et al., 2003).
Entity Ovarian carcinoma
Disease BRMS1 mRNA expression in ovarian carcinoma was found to be significantly lower than in normal ovarian tissue. Transfection of BRMS1 into the metastatic ovarian cancer cell line HO-8910PM significantly suppressed call adhesion to extracellular matrix components. In addition, when injected into nude mice the BRMS1-transfected cells had a reduced capacity to form lung colonies (Zhang et al., 2006). This suggests that BRMS1 may play a role in the metastatic potential of ovarian tumours.
Entity Melanoma
Disease BRMS1 mRNA expression has been observed in melanocytes, shown to be reduced in early melanoma-derived cell lines, and scarcely detectable in metastatic cell lines. Transfection of BRMS1 into metastatic melanoma cell lines significantly reduced the metastatic potential while having no effect on tumourigenicity (Shevde et al., 2002).


Dissemination and growth of cancer cells in metastatic sites
Chambers AF, Groom AC, MacDonald IC.
Nat Rev Cancer. 2002 Aug;2(8):563-72.
PMID 12154349
Breast cancer metastasis suppressor 1 inhibits gene expression by targeting nuclear factor-kappaB activity
Cicek M, Fukuyama R, Welch DR, Sizemore N, Casey G.
Cancer Res. 2005 May 1;65(9):3586-95.
PMID 15867352
Metastasis suppression by breast cancer metastasis suppressor 1 involves reduction of phosphoinositide signaling in MDA-MB-435 breast carcinoma cells.
DeWald DB, Torabinejad J, Samant RS, Johnston D, Erin N, Shope JC, Xie Y, Welch DR.
Cancer Res. 2005 Feb 1;65(3):713-7.
PMID 15705865
Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report.
Duffy MJ, O'Grady P, Devaney D, O'Siorain L, Fennelly JJ, Lijnen HJ.
Cancer. 1988 Aug 1;62(3):531-3.
PMID 3134120
Urokinase-plasminogen activator, a new and independent prognostic marker in breast cancer.
Duffy MJ, Reilly D, O'Sullivan C, O'Higgins N, Fennelly JJ, Andreasen P.
Cancer Res. 1990 Nov 1;50(21):6827-9.Click here to read
PMID 2119883
The biochemistry of metastasis.
Duffy MJ.
Adv Clin Chem. 1996;32:135-66. (Review)
PMID 8899072
Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.
Hicks DG, Yoder BJ, Short S, Tarr S, Prescott N, Crowe JP, Dawson AE, Budd GT, Sizemore S, Cicek M, Choueiri TK, Tubbs RR, Gaile D, Nowak N, Accavitti-Loper MA, Frost AR, Welch DR, Casey G.
Clin Cancer Res. 2006 Nov 15;12(22):6702-8.
PMID 17121889
Breast cancer metastasis suppressor 1 (BRMS1) is stabilized by the Hsp90 chaperone.
Hurst DR, Mehta A, Moore BP, Phadke PA, Meehan WJ, Accavitti MA, Shevde LA, Hopper JE, Xie Y, Welch DR, Samant RS.
Biochem Biophys Res Commun. 2006 Oct 6;348(4):1429-35. Epub 2006 Aug 10.
PMID 16919237
Expression of the breast cancer metastasis suppressor gene, BRMS1, in human breast carcinoma: lack of correlation with metastasis to axillary lymph nodes.
Kelly LM, Buggy Y, Hill A, O'Donovan N, Duggan C, McDermott EW, O'Higgins NJ, Young L, Duffy MJ.
Tumour Biol. 2005 Jul-Aug;26(4):213-6. Epub 2005 Jul 6.
PMID 16006775
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients.
Look MP, van Putten WL, Duffy MJ, Harbeck N, Christensen IJ, Thomssen C, Kates R, Spyratos F, Ferno M, Eppenberger-Castori S, Sweep CG, Ulm K, Peyrat JP, Martin PM, Magdelenat H, Brunner N, Duggan C, Lisboa BW, Bendahl PO, Quillien V, Daver A, Ricolleau G, Meijer-van Gelder ME, Manders P, Fiets WE, Blankenstein MA, Broet P, Romain S, Daxenbichler G, Windbichler G, Cufer T, Borstnar S, Kueng W, Beex LV, Klijn JG, O'Higgins N, Eppenberger U, Janicke F, Schmitt M, Foekens JA.
J Natl Cancer Inst. 2002 Jan 16;94(2):116-28.
PMID 11792750
Breast cancer metastasis suppressor 1 (BRMS1) forms complexes with retinoblastoma-binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription.
Meehan WJ, Samant RS, Hopper JE, Carrozza MJ, Shevde LA, Workman JL, Eckert KA, Verderame MF, Welch DR.
J Biol Chem. 2004 Jan 9;279(2):1562-9. Epub 2003 Oct 26.
PMID 14581478
Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer.
Metge BJ, Frost AR, King JA, Dyess DL, Welch DR, Samant RS, Shevde LA.
Clin Exp Metastasis. 2008;25(7):753-63. Epub 2008 Jun 20.
PMID 18566899
Epigenetic gene silencing in cancer initiation and progression.
Nephew KP, Huang TH.
Cancer Lett. 2003 Feb 20;190(2):125-33.
PMID 12565166
The prognostic value of the soluble urokinase-type plasminogen activator receptor (s-uPAR) in plasma of breast cancer patients with and without metastatic disease.
Nijziel MR, Van Oerle R, Hellenbrand D, Van Pampus EC, Hillen HF, Hamulyak K.
J Thromb Haemost. 2003 May;1(5):982-6.
PMID 12871365
Identification of a novel BRMS1-homologue protein p40 as a component of the mSin3A/p33(ING1b)/HDAC1 deacetylase complex.
Nikolaev AY, Papanikolaou NA, Li M, Qin J, Gu W.
Biochem Biophys Res Commun. 2004 Oct 29;323(4):1216-22.
PMID 15451426
Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription by abrogating NF-kappaB activation.
Samant RS, Clark DW, Fillmore RA, Cicek M, Metge BJ, Chandramouli KH, Chambers AF, Casey G, Welch DR, Shevde LA.
Mol Cancer. 2007 Jan 16;6:6.
PMID 17227585
Suppression of murine mammary carcinoma metastasis by the murine ortholog of breast cancer metastasis suppressor 1 (Brms1).
Samant RS, Debies MT, Hurst DR, Moore BP, Shevde LA, Welch DR.
Cancer Lett. 2006 Apr 28;235(2):260-5. Epub 2005 Jun 22.
PMID 15978719
Analysis of mechanisms underlying BRMS1 suppression of metastasis.
Samant RS, Seraj MJ, Saunders MM, Sakamaki TS, Shevde LA, Harms JF, Leonard TO, Goldberg SF, Budgeon L, Meehan WJ, Winter CR, Christensen ND, Verderame MF, Donahue HJ, Welch DR.
Clin Exp Metastasis. 2000;18(8):683-93.
PMID 11827072
Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication.
Saunders MM, Seraj MJ, Li Z, Zhou Z, Winter CR, Welch DR, Donahue HJ.
Cancer Res. 2001 Mar 1;61(5):1765-7.
PMID 11280719
Functional evidence for a novel human breast carcinoma metastasis suppressor, BRMS1, encoded at chromosome 11q13.
Seraj MJ, Samant RS, Verderame MF, Welch DR.
Cancer Res. 2000 Jun 1;60(11):2764-9.
PMID 10850410
Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1.
Shevde LA, Samant RS, Goldberg SF, Sikaneta T, Alessandrini A, Donahue HJ, Mauger DT, Welch DR.
Exp Cell Res. 2002 Feb 15;273(2):229-39.
PMID 11822878
Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases.
Stark AM, Tongers K, Maass N, Mehdorn HM, Held-Feindt J.
J Cancer Res Clin Oncol. 2005 Mar;131(3):191-8. Epub 2004 Dec 8.
PMID 15592684
Molecular biology of breast cancer metastasis. Genetic regulation of human breast carcinoma metastasis.
Welch DR, Steeg PS, Rinker-Schaeffer CW.
Breast Cancer Res. 2000;2(6):408-16. Epub 2000 Jul 21.
PMID 11250734
Suppression of human ovarian carcinoma metastasis by the metastasis-suppressor gene, BRMS1.
Zhang S, Lin QD, DI W.
Int J Gynecol Cancer. 2006 Mar-Apr;16(2):522-31.
PMID 16681721
Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer.
Zhang Z, Yamashita H, Toyama T, Yamamoto Y, Kawasoe T, Iwase H.
Clin Cancer Res. 2006 Nov 1;12(21):6410-4.
PMID 17085653


This paper should be referenced as such :
Buggy, Y ; Duffy, MJ
BRMS1 (breast cancer metastasis suppressor 1)
Atlas Genet Cytogenet Oncol Haematol. 2009;13(11):780-783.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)BRMS1   17262
Entrez_Gene (NCBI)BRMS1    BRMS1 transcriptional repressor and anoikis regulator
GeneCards (Weizmann)BRMS1
Ensembl hg19 (Hinxton)ENSG00000174744 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000174744 [Gene_View]  ENSG00000174744 [Sequence]  chr11:66337339-66345104 [Contig_View]  BRMS1 [Vega]
ICGC DataPortalENSG00000174744
TCGA cBioPortalBRMS1
Genatlas (Paris)BRMS1
SOURCE (Princeton)BRMS1
Genetics Home Reference (NIH)BRMS1
Genomic and cartography
GoldenPath hg38 (UCSC)BRMS1  -     chr11:66337339-66345104 -  11q13.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)BRMS1  -     11q13.2   [Description]    (hg19-Feb_2009)
GoldenPathBRMS1 - 11q13.2 [CytoView hg19]  BRMS1 - 11q13.2 [CytoView hg38]
Genome Data Viewer NCBIBRMS1 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AF147350 AF159141 AI797564 AK310991 AK313773
RefSeq transcript (Entrez)NM_001024957 NM_001024958 NM_015399
Consensus coding sequences : CCDS (NCBI)BRMS1
Gene ExpressionBRMS1 [ NCBI-GEO ]   BRMS1 [ EBI - ARRAY_EXPRESS ]   BRMS1 [ SEEK ]   BRMS1 [ MEM ]
Gene Expression Viewer (FireBrowse)BRMS1 [ Firebrowse - Broad ]
GenevisibleExpression of BRMS1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)25855
GTEX Portal (Tissue expression)BRMS1
Human Protein AtlasENSG00000174744-BRMS1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ9HCU9   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ9HCU9  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ9HCU9
Domains : Interpro (EBI)Sds3   
Domain families : Pfam (Sanger)Sds3 (PF08598)   
Domain families : Pfam (NCBI)pfam08598   
Domain families : Smart (EMBL)Sds3 (SM01401)  
Conserved Domain (NCBI)BRMS1
PDB Europe2XUS    4AUV   
PDB (PDBSum)2XUS    4AUV   
PDB (IMB)2XUS    4AUV   
Structural Biology KnowledgeBase2XUS    4AUV   
SCOP (Structural Classification of Proteins)2XUS    4AUV   
CATH (Classification of proteins structures)2XUS    4AUV   
AlphaFold pdb e-kbQ9HCU9   
Human Protein Atlas [tissue]ENSG00000174744-BRMS1 [tissue]
Protein Interaction databases
IntAct (EBI)Q9HCU9
Complex Portal (EBI)Q9HCU9 CPX-3322 SIN3B histone deacetylase complex
Q9HCU9 CPX-3323 SIN3A histone deacetylase complex, ES cell-specific variant
Q9HCU9 CPX-3321 SIN3A histone deacetylase complex
Ontologies - Pathways
Ontology : AmiGOnegative regulation of transcription by RNA polymerase II  protein binding  nucleus  nucleoplasm  cytoplasm  apoptotic process  histone deacetylation  negative regulation of NF-kappaB transcription factor activity  histone deacetylase binding  regulation of apoptotic process  negative regulation of transcription, DNA-templated  NF-kappaB binding  Sin3-type complex  positive regulation of protein deacetylation  positive regulation of anoikis  
Ontology : EGO-EBInegative regulation of transcription by RNA polymerase II  protein binding  nucleus  nucleoplasm  cytoplasm  apoptotic process  histone deacetylation  negative regulation of NF-kappaB transcription factor activity  histone deacetylase binding  regulation of apoptotic process  negative regulation of transcription, DNA-templated  NF-kappaB binding  Sin3-type complex  positive regulation of protein deacetylation  positive regulation of anoikis  
REACTOMEQ9HCU9 [protein]
REACTOME PathwaysR-HSA-3214815 [pathway]   
NDEx NetworkBRMS1
Atlas of Cancer Signalling NetworkBRMS1
Wikipedia pathwaysBRMS1
Orthology - Evolution
GeneTree (enSembl)ENSG00000174744
Phylogenetic Trees/Animal Genes : TreeFamBRMS1
Homologs : HomoloGeneBRMS1
Homology/Alignments : Family Browser (UCSC)BRMS1
Gene fusions - Rearrangements
Fusion : QuiverBRMS1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerBRMS1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)BRMS1
Exome Variant ServerBRMS1
GNOMAD BrowserENSG00000174744
Varsome BrowserBRMS1
ACMGBRMS1 variants
Genomic Variants (DGV)BRMS1 [DGVbeta]
DECIPHERBRMS1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisBRMS1 
ICGC Data PortalBRMS1 
TCGA Data PortalBRMS1 
Broad Tumor PortalBRMS1
OASIS PortalBRMS1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICBRMS1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DBRMS1
Mutations and Diseases : HGMDBRMS1
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)BRMS1
DoCM (Curated mutations)BRMS1
CIViC (Clinical Interpretations of Variants in Cancer)BRMS1
NCG (London)BRMS1
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry BRMS1
NextProtQ9HCU9 [Medical]
Target ValidationBRMS1
Huge Navigator BRMS1 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDBRMS1
Pharm GKB GenePA164741342
Clinical trialBRMS1
DataMed IndexBRMS1
PubMed112 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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