title: HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression.
abstract: Cell-cell adhesion molecule cadherin-11(CDH11) is preferentially expressed in basal-like breast cancer cells and facilitates breast cancer cell migration by promoting small GTPase Rac activity. However, how the expression of CDH11 is regulated in breast cancer cells is not understood. Here, we show that CDH11 is transcriptionally controlled by homeobox C8 (HOXC8) in human breast cancer cells. HOXC8 serves as a CDH11-specific transcription factor and binds to the site of nucleotides -196 to -191 in the CDH11 promoter. Depletion of HOXC8 leads to the decrease in anchorage-independent cell growth, cell migration/invasion and spontaneous metastasis of breast cancer cells; however, suppressed tumorigenic events were fully rescued by ectopic CDH11 expression in HOXC8-knockdown cells. These results indicate that HOXC8 impacts breast tumorigenesis through CDH11. The analysis of publically available human breast tumor microarray gene expression database demonstrates a strong positive linear association between HOXC8 and CDH11 expression ( = 0.801, p < 0.001). Survival analysis (Kaplan-Meier method, log-rank test) show that both high HOXC8 and CDH11 expression correlate with poor recurrence-free survival rate of patients. Together, our study suggests that HOXC8 promotes breast tumorigenesis by maintaining high level of CDH11 expression in breast cancer cells.
authors.affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei, Anhui, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Fengmei
authors.initials: F
authors.lastname: Chao
authors.forename: Bei
authors.initials: B
authors.lastname: Huang
authors.forename: Dahai
authors.initials: D
authors.lastname: Liu
authors.forename: Jaejik
authors.initials: J
authors.lastname: Kim
authors.forename: Shuang
authors.initials: S
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C086960:osteoblast cadherin; D008156:Luciferases