Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients
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Autor:innen
Kohler, Reto
Anugraham, Merrina
Nunez Lopez, Monica
Xiao, Christina
Schoetzau, Andreas
Fedier, André
Jacob, Francis
Heinzelmann-Schwarz, Viola
Autor:in (Körperschaft)
Publikationsdatum
12.07.2016
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Ãœbergeordnetes Werk
Oncotarget
Themenheft
Reihe / Serie
Jahrgang / Band
7
Ausgabe / Nummer
32
Seiten / Dauer
51674
Patentnummer
Verlag / Herausgebende Institution
Impact Journals LLC
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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
Schlagwörter
dna methylation, n-glycosylation, bisecting glcnac, long-time survival, ovarian cancer
Fachgebiet (DDC)
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1949-2553
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Lizenz
Zitation
KOHLER, Reto, Merrina ANUGRAHAM, Monica NUNEZ LOPEZ, Christina XIAO, Andreas SCHOETZAU, Timm HETTICH, Götz SCHLOTTERBECK, André FEDIER, Francis JACOB und Viola HEINZELMANN-SCHWARZ, 2016. Epigenetic activation of MGAT3 and corresponding bisecting GlcNAc shortens the survival of cancer patients. Oncotarget. 12 Juli 2016. Bd. 7, Nr. 32, S. 51674. DOI 10.18632/oncotarget.10543. Verfügbar unter: http://hdl.handle.net/11654/23407