Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients

Loading...
Thumbnail Image
Authors
Kohler, Reto
Anugraham, Merrina
Nunez Lopez, Monica
Xiao, Christina
Schoetzau, Andreas
Fedier, André
Jacob, Francis
Heinzelmann-Schwarz, Viola
Author (Corporation)
Publication date
12.07.2016
Typ of student thesis
Course of study
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Oncotarget
Special issue
DOI of the original publication
Series
Series number
Volume
7
Issue / Number
32
Pages / Duration
51674
Patent number
Publisher / Publishing institution
Impact Journals LLC
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
Abstract
Bisecting GlcNAc on N-glycoproteins is described in E-cadherin-, EGF-, Wnt- and integrin- cancer-associated signaling pathways. However, the mechanisms regulating bisecting GlcNAc expression are not clear. Bisecting GlcNAc is attached to N-glycans through beta 1-4 N-acetylglucosaminyl transferase III (MGAT3), which is encoded by two exons flanked by high-density CpG islands. Despite a recently described correlation of MGAT3 and bisecting GlcNAc in ovarian cancer cells, it remains unknown whether DNA methylation is causative for the presence of bisecting GlcNAc. Here, we narrow down the regulatory genomic region and show that reconstitution of MGAT3 expression with 5-Aza coincides with reduced DNA methylation at the MGAT3 transcription start site. The presence of bisecting GlcNAc on released N-glycans was detected by mass spectrometry (LC-ESI-qTOF-MS/MS) in serous ovarian cancer cells upon DNA methyltransferase inhibition. The regulatory impact of DNA methylation on MGAT3 was further evaluated in 18 TCGA cancer types (n = 6118 samples) and the results indicate an improved overall survival in patients with reduced MGAT3 expression, thereby identifying long-term survivors of high-grade serous ovarian cancers (HGSOC). Epigenetic activation of MGAT3 was also confirmed in basal-like breast cancers sharing similar molecular and genetic features with HGSOC. These results provide novel insights into the epigenetic regulation of MGAT3/bisecting
Keywords
dna methylation, n-glycosylation, bisecting glcnac, long-time survival, ovarian cancer
Subject (DDC)
Project
Event
Exhibition start date
Exhibition end date
Conference start date
Conference end date
Date of the last check
ISBN
ISSN
1949-2553
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
License
Citation
Kohler, R., Anugraham, M., Nunez Lopez, M., Xiao, C., Schoetzau, A., Hettich, T., Schlotterbeck, G., Fedier, A., Jacob, F., & Heinzelmann-Schwarz, V. (2016). Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients. Oncotarget, 7(32), 51674. https://doi.org/10.18632/oncotarget.10543