title: Forkhead box protein k1 recruits TET1 to act as a tumor suppressor and is associated with MRI detection.
abstract: OBJECTIVE
  Today, more and more evidence suggests that Foxk proteins (Foxk1 and Foxk2) work as transcriptional repressors in different kinds of cancer, but whether Foxk1 has a role in mediating tumorigenesis in breast cancer, the evidence is rare.
  
  
  METHODS
  MCF-7 cells transfected with shFoxk1 displayed a mesenchymal morphology and reduced the expression of E-cadherin, and increased the expression of N-cadherin. Transwell invasion assay and living imaging assay show that the overexpression of Foxk1 could inhibit metastasis in vitro and in vivo. Ribonucleic acid sequencing revealed that the knockdown of Foxk1 resulted in the up-regulation of different oncogenes, which was implicated in metastasis and tumor angiopoiesis. Quantitative chromatin immunoprecipitation, chromatin immunoprecipitation and Luciferase reporter assays suggested that Foxk1 could bind to the promoter of epithelial-mesenchymal transition inducer Twist and vascular endothelial growth factor, VEGF. Mass Spectrometry, co-immunoprecipitation assays and glutathione-S-transferase pull-down assay detected that Foxk1 was physically associated with Ten-eleven translocation 1, TET1, in vivo and in vitro.
  
  
  RESULTS
  We reported that the mean expression level of Foxk1 in breast cancer was significantly lower than the adjacent noncarcinoma tissue. The higher Foxk1 expression was associated with better prognosis. Endothelial tube formation assays indicated that Foxk1 might regulate breast cancer angiogenesis through transcriptional repression of vascular endothelial growth factor. Furthermore, in vivo magnetic resonance imaging revealed the overexpression of Foxk1 could enhance the detection of the tumors. Further, a strong negative correlation was observed between Foxk1 and Twsit or between Foxk1 and vascular endothelial growth factor, and the higher Foxk1 expression is correlated with better over all survivals and better relapse-free survivals.
  
  
  CONCLUSIONS
  Together, our data indicated the function of Foxk1 as a tumor suppressor in facilitating angiogenesis and metastasis in breast cancer.
authors.affiliation: Department of Radiology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai.
authors.forename: Taotao
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Rheumatology, Gansu Provincial Hospital, Lanzhou, Gansu.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Ningbo NO.7 Hospital, Ningbo, Zhejiang.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Radiology, International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai shenzihai1101@126.com zhaoxiaqian002@126.com.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Cardiology, Ningbo NO.7 Hospital, Ningbo, Zhejiang shenzihai1101@126.com zhaoxiaqian002@126.com.
authors.forename: Caijie
authors.initials: C
authors.lastname: Shen
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008279:Magnetic Resonance Imaging; D006899:Mixed Function Oxygenases; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; C495879:FOXK1 protein, human; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C103173:TWIST1 protein, human; D025521:Tumor Suppressor Proteins; D051879:Twist-Related Protein 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human
keywords: Foxk1; TET1; Twist; VEGF; tumor suppressor