2016
DOI: 10.18632/oncotarget.7039
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Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism

Abstract: Metabolic networks are highly connected and complex, but a single enzyme, O-GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179). Metabolic profiling revealed decreased glucose consumption and lactate production after OGT inhi… Show more

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Cited by 77 publications
(69 citation statements)
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“…GFAT1 is ubiquitously expressed and GFAT2 is expressed in some tissues like heart, skeletal muscle, lung, and placenta, besides its elevated expression in the central nervous system (DeHaven et al, 2001). Although the relevance of HBP in cancer metabolism has been described in some types of carcinomas such as prostrate (Itkonen et al, 2016), lung (Alisson-Silva et al, 2013), breast (Chanmee et al, 2016), pancreas (Itkonen et al, 2016), and colon (Steenackers et al, 2016), the regulation of this pathway remains largely unknown in tumor cells. Although the relevance of HBP in cancer metabolism has been described in some types of carcinomas such as prostrate (Itkonen et al, 2016), lung (Alisson-Silva et al, 2013), breast (Chanmee et al, 2016), pancreas (Itkonen et al, 2016), and colon (Steenackers et al, 2016), the regulation of this pathway remains largely unknown in tumor cells.…”
Section: Hbp Is Emerging As An Important Branch Of Glc Metabolism Inmentioning
confidence: 99%
“…GFAT1 is ubiquitously expressed and GFAT2 is expressed in some tissues like heart, skeletal muscle, lung, and placenta, besides its elevated expression in the central nervous system (DeHaven et al, 2001). Although the relevance of HBP in cancer metabolism has been described in some types of carcinomas such as prostrate (Itkonen et al, 2016), lung (Alisson-Silva et al, 2013), breast (Chanmee et al, 2016), pancreas (Itkonen et al, 2016), and colon (Steenackers et al, 2016), the regulation of this pathway remains largely unknown in tumor cells. Although the relevance of HBP in cancer metabolism has been described in some types of carcinomas such as prostrate (Itkonen et al, 2016), lung (Alisson-Silva et al, 2013), breast (Chanmee et al, 2016), pancreas (Itkonen et al, 2016), and colon (Steenackers et al, 2016), the regulation of this pathway remains largely unknown in tumor cells.…”
Section: Hbp Is Emerging As An Important Branch Of Glc Metabolism Inmentioning
confidence: 99%
“…Various studies demonstrate a therapeutic window may exist to specifically target OGT and O-GlcNAcylation in cancer cells 39; 40; 80 . A number of novel chemicals have been developed to target OGT and reduce O-GlcNAcylation in mammalian cells.…”
Section: Introductionmentioning
confidence: 99%
“…In the past 10 years, Walker and colleagues 81; 82 have developed a number of OGT inhibitors aimed at providing insights to the biological and structural function of the enzyme in mammalian cells. Namely, the commercially available small molecule inhibitor ST045849, has been recently shown to stimulate cell death in prostate cancer cells when used in combination with alanine amidotransferase inhibitors 80 .…”
Section: Introductionmentioning
confidence: 99%
“…The O -GlcNAcylation of specific proteins could modulate their structure and function and thus influence signaling cascades, antioxidant defenses, et al [912]. Up to now, there are numerous reports on O -GlcNAcylation of cytosolic, nuclear and mitochondrial proteins distributed in various tissues [1315].…”
Section: Introductionmentioning
confidence: 99%