GalNAc-T4 putatively modulates the estrogen regulatory network through FOXA1 glycosylation in human breast cancer cells
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  • 作者:Bachir Niang ; Liyuan Jin ; Xixi Chen ; Xiaohan Guo…
  • 关键词:GALNT4 ; O ; Glycosylation ; ERα ; FOXA1 ; Vicia Villosa Lectin (VVL)
  • 刊名:Molecular and Cellular Biochemistry
  • 出版年:2016
  • 出版时间:January 2016
  • 年:2016
  • 卷:411
  • 期:1-2
  • 页码:393-402
  • 全文大小:2,432 KB
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  • 作者单位:Bachir Niang (1)
    Liyuan Jin (1)
    Xixi Chen (1)
    Xiaohan Guo (1)
    Hongshuo Zhang (1)
    Qiong Wu (2)
    Arshad Ahmed Padhiar (1)
    Min Xiao (3)
    Deyu Fang (4)
    Jianing Zhang (1) (2)

    1. Department of Biochemistry, Institute of Glycobiology, Dalian Medical University, 9 South Lvshun Road Western Section, Dalian, 116044, China
    2. School of Life Science and Medicine, Dalian University of Technology, 2 Linggong Road, Dalian, 116024, China
    3. National Glycoengineering Research Center and State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, China
    4. Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Ave, Chicago, IL, 60611, USA
  • 刊物类别:Biomedical and Life Sciences
  • 刊物主题:Life Sciences
    Biochemistry
    Medical Biochemistry
    Oncology
    Cardiology
  • 出版者:Springer Netherlands
  • ISSN:1573-4919
文摘
GALNT4 belongs to a family of N-acetylgalactosaminyltransferases, which catalyze the transfer of GalNAc to Serine or Threonine residues in the initial step of mucin-type O-linked protein glycosylation. This glycosylation type is the most complex post-translational modification of proteins, playing important roles during cellular differentiation and in pathological disorders. Most of the breast cancer subtypes are estrogen receptor positive, and hence, the estrogen pathway represents a key regulatory network. We investigated the expression of GalNAc-T4 in a panel of mammary epithelial cell lines and found its expression is associated with the estrogen status of the cells. FOXA1, a key transcription factor, functions to promote estrogen responsive gene expression by acting as a cofactor to estrogen receptor alpha (ERα), but all the aspects of this regulatory mechanism are not fully explored. This study found that knockdown of GALNT4 expression in human breast cancer cells attenuated the protein expression of ERα, FOXA1, and Cyclin D1. Further, our immunoprecipitation assays depicted the possibility of FOXA1 to undergo O-GalNAc modifications with a decrease of GalNAc residues in the GALNT4 knockdown cells and also impairment in the FOXA1–ERα association. Rescuing GALNT4 expression could restore the interaction as well as the glycosylation of FOXA1. Together, these findings suggest a key role for GalNAc-T4 in the estrogen pathway through FOXA1 glycosylation. Keywords GALNT4 O-Glycosylation ERα FOXA1 Vicia Villosa Lectin (VVL)

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