BCAR4 Gene

Name breast cancer anti-estrogen resistance 4 (non-protein coding)
Description This gene produces a spliced long non-coding RNA (lncRNA) that has been implicated in breast cancer metastasis. It was originally identified in a screen for genes responsible for the development of resistance to anti-estrogens in breast cancer cells. It is thought that release of CCL21 enables this lncRNA to bind to the SNIP1 and PNUTS transcription factors, thereby activating a non-canonical GLI-dependent hedgehog signaling pathway that promotes cancer cell migration and invasion. A similar gene in cow expresses a protein in mature oocytes and preimplantation embryos. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2015]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Emerging evidence from multiple studies demonstrates that the long noncoding RNA BCAR4 exerts multifaceted oncogenic functions in a variety of human cancers, particularly in breast cancer. Initially identified as a mediator of antiestrogen resistance that promotes endocrine escape and anchorage‐independent growth"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", BCAR4 has since been shown to drive tumor cell proliferation, metastasis, and altered cellular metabolism. In breast tumors, for example, BCAR4 promotes metastasis by binding to transcriptional regulators such as SNIP1 and PNUTS, a process that relieves repression on p300‐dependent histone acetylation and ultimately activates a noncanonical Hedgehog/GLI2 transcriptional program that enhances cell migration and invasiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " BCAR4 is also implicated in metabolic reprogramming; it is required for YAP‐dependent glycolysis via the coordination of Hedgehog signaling to upregulate key glycolytic activators, thereby linking oncogenic signaling with altered energy metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, BCAR4 contributes to tamoxifen resistance by activating ERBB2/ERBB3 signaling, with its elevated expression correlating with poor progression‐free and overall survival, which underscores its potential as a therapeutic target—interventions using locked nucleic acids or ERBB‐targeted agents have been shown to counteract its oncogenic effects."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Collectively, these studies highlight BCAR4 as a critical regulator of transcriptional modulation, signal transduction, and metabolic adaptation in tumor progression, thereby establishing it as a promising prognostic biomarker and potential candidate for targeted cancer therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Danielle Meijer, Ton van Agthoven, Peter T Bosma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional screen for genes responsible for tamoxifen resistance in human breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-05-0156"}], "href": "https://doi.org/10.1158/1541-7786.MCR-05-0156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16778085"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16778085"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhen Xing, Aifu Lin, Chunlai Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "lncRNA directs cooperative epigenetic regulation downstream of chemokine signals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2014.10.013"}], "href": "https://doi.org/10.1016/j.cell.2014.10.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25416949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25416949"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Fenyong Chen, Jiadong Mo, Li Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Long noncoding RNA BCAR4 promotes osteosarcoma progression through activating GLI2-dependent gene transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-016-5256-y"}], "href": "https://doi.org/10.1007/s13277-016-5256-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27460090"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27460090"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xin Zheng, Han Han, Guang-Ping Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201797609"}], "href": "https://doi.org/10.15252/embj.201797609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28963395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28963395"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "M F E Godinho, A M Sieuwerts, M P Look, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6605884"}], "href": "https://doi.org/10.1038/sj.bjc.6605884"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20859285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20859285"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M F E Godinho, J D Wulfkuhle, M P Look, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCAR4 induces antioestrogen resistance but sensitises breast cancer to lapatinib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2012.351"}], "href": "https://doi.org/10.1038/bjc.2012.351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22892392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22892392"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ton van Agthoven, Lambert C J Dorssers, Ulrich Lehmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) Drives Proliferation of IPH-926 lobular Carcinoma Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0136845"}], "href": "https://doi.org/10.1371/journal.pone.0136845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26317614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26317614"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Qiong Yi, Zhongcheng Liu, Kun Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of long non-coding RNA BCAR4 in human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13577-021-00556-6"}], "href": "https://doi.org/10.1007/s13577-021-00556-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34041673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34041673"}]}]}]}
NCBI Gene ID 400500
API
Download Associations
Predicted Functions View BCAR4's ARCHS4 Predicted Functions.
Co-expressed Genes View BCAR4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View BCAR4's ARCHS4 Predicted Functions.

Functional Associations

BCAR4 has 532 functional associations with biological entities spanning 7 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, cell line, cell type or tissue, gene, protein or microRNA) extracted from 22 datasets.

Click the + buttons to view associations for BCAR4 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of BCAR4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of BCAR4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of BCAR4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with BCAR4 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of BCAR4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of BCAR4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of BCAR4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with BCAR4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with BCAR4 gene/protein from the curated CTD Gene-Disease Associations dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of BCAR4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of BCAR4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with BCAR4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of BCAR4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of BCAR4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of BCAR4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of BCAR4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of BCAR4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of BCAR4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of BCAR4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of BCAR4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of BCAR4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of BCAR4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.