title: Embigin, regulated by HOXC8, plays a suppressive role in breast tumorigenesis.
abstract: The transmembrane glycoprotein embigin (EMB) belongs to the immunoglobulin superfamily (IgSF) and a number of IgSF members have been identified as biomarkers for cancer progression. In this study, we show that embigin is transcriptionally regulated by Homeobox C8 (HOXC8) in breast cancer cells and embigin expression suppresses breast tumorigenesis. With aid of Western blot, luciferase reporter gene assay and chromatin immunoprecipitation, we reveal that HOXC8 binds to the EMB promoter at the region of nucleotides -2303 to -2315 and acts as a transcription inhibitor to suppress embigin expression. Depletion of embigin leads to increase in proliferation, anchorage-independent growth and migration of breast cancer cells, and the inhibitory effects mediated by HOXC8 knockdown on breast tumorigenesis can be largely rescued by depletion of embigin expression in breast cancer cells, suggesting that HOXC8 regulates breast tumorigenesis, at least partly, through regulating embigin expression. Moreover, we show that loss of embigin promotes proliferation, anchorage-independent growth, and migration ability of normal mammary epithelial MCF10A cells. The analyses of publically available human breast tumor microarray gene expression database show that low embigin levels correlate with short survival of breast tumor patients, particularly with basal-like tumor patients, and embigin expression is low specifically in patients with basal-like, ER-/HER2- tumors. Taken together, our study demonstrates that low/loss of embigin plays an important role in the progression of breast tumors.
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Chao
authors.affiliation: Anhui University, School of Life Sciences, Hefei, Anhui Province, P. R. China.|The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Science, Southeast University, Nanjing, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Houli
authors.initials: H
authors.lastname: Liu
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Anhui University, School of Life Sciences, Hefei, Anhui Province, P. R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Anhui University, School of Life Sciences, Hefei, Anhui Province, P. R. China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Anhui University, School of Life Sciences, Hefei, Anhui Province, P. R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wen
authors.affiliation: Anhui University, School of Life Sciences, Hefei, Anhui Province, P. R. China.
authors.forename: Kaiye
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Huang
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Daihai
authors.initials: D
authors.lastname: Liu
authors.affiliation: Anhui University, School of Life Sciences, Center for Stem Cell and Translational Medicine, Hefei, Anhui Province, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D061986:MCF-7 Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic
chemical_list: D014408:Biomarkers, Tumor; C069503:EMB protein, human; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones
keywords: EMB; HOXC8; breast cancer; transcription; tumorigenesis