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Cited by 292

The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells

Itkonen, Harri M., Minner, Sarah, Guldvik, Ingrid J., Sandmann, Mareike Julia, Tsourlakis, Maria Christina, Berge, Viktor, Svindland, Aud, Schlomm, Thorsten, Mills, Ian G.·2013·Cancer Research

Abstract

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference–mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the principal effects of OGT inhibition in prostate cancer cells were related to cell-cycle progression and DNA replication. In particular, c-MYC was identified as a candidate upstream regulator of OGT target genes and OGT inhibition elicited a dose-dependent decrease in the levels of c-MYC protein but not c-MYC mRNA in cell lines. Supporting this relationship, expression of c-MYC and OGT was tightly correlated in human prostate cancer samples (n = 1306). Our findings identify HBP as a modulator of prostate cancer growth and c-MYC as a key target of OGT function in prostate cancer cells. Cancer Res; 73(16); 5277–87. ©2013 AACR.

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Metadata

Authors
Itkonen, H. M., Minner, S., Guldvik, I. J., Sandmann, M. J., Tsourlakis, M. C., Berge, V., Svindland, A., Schlomm, T., & Mills, I. G.
Venue
Cancer Research
Published
2013-08-13
Volume
73
Issue
16
Pages
5277-5287
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2134468405
Cited by
292
References
10
FWCI
8.07
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells. https://app.cochat.ai/papers/10.1158/0008-5472.can-13-0549
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Itkonen, H. M., Minner, S., Guldvik, I. J., Sandmann, M. J., Tsourlakis, M. C., Berge, V., Svindland, A., Schlomm, T., & Mills, I. G. (2013). O-GlcNAc Transferase Integrates Metabolic Pathways to Regulate the Stability of c-MYC in Human Prostate Cancer Cells. Cancer Research. https://doi.org/10.1158/0008-5472.can-13-0549

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