| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-109 |
Sentence |
denotes |
Hyper-O-GlcNAcylation is anti-apoptotic and maintains constitutive NF-κB activity in pancreatic cancer cells. |
| T2 |
110-346 |
Sentence |
denotes |
Cancer cell metabolic reprogramming includes a shift in energy production from oxidative phosphorylation to less efficient glycolysis even in the presence of oxygen (Warburg effect) and use of glutamine for increased biosynthetic needs. |
| T3 |
347-475 |
Sentence |
denotes |
This necessitates greatly increased glucose and glutamine uptake, both of which enter the hexosamine biosynthetic pathway (HBP). |
| T4 |
476-670 |
Sentence |
denotes |
The HBP end product UDP-N-acetylglucosamine (UDP-GlcNAc) is used in enzymatic post-translational modification of many cytosolic and nuclear proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). |
| T5 |
671-783 |
Sentence |
denotes |
Here, we observed increased HBP flux and hyper-O-GlcNAcylation in human pancreatic ductal adenocarcinoma (PDAC). |
| T6 |
784-904 |
Sentence |
denotes |
PDAC hyper-O-GlcNAcylation was associated with elevation of OGT and reduction of the enzyme that removes O-GlcNAc (OGA). |
| T7 |
905-1122 |
Sentence |
denotes |
Reducing hyper-O-GlcNAcylation had no effect on non-transformed pancreatic epithelial cell growth, but inhibited PDAC cell proliferation, anchorage-independent growth, orthotopic tumor growth, and triggered apoptosis. |
| T8 |
1123-1185 |
Sentence |
denotes |
PDAC is supported by oncogenic NF-κB transcriptional activity. |
| T9 |
1186-1267 |
Sentence |
denotes |
The NF-κB p65 subunit and upstream kinases IKKα/IKKβ were O-GlcNAcylated in PDAC. |
| T10 |
1268-1440 |
Sentence |
denotes |
Reducing hyper-O-GlcNAcylation decreased PDAC cell p65 activating phosphorylation (S536), nuclear translocation, NF-κB transcriptional activity, and target gene expression. |
| T11 |
1441-1669 |
Sentence |
denotes |
Conversely, mimicking PDAC hyper-O-GlcNAcylation through pharmacological inhibition of OGA suppressed suspension culture-induced apoptosis and increased IKKα and p65 O-GlcNAcylation, accompanied by activation of NF-κB signaling. |
| T12 |
1670-1841 |
Sentence |
denotes |
Finally, reducing p65 O-GlcNAcylation specifically by mutating two p65 O-GlcNAc sites (T322A and T352A) attenuated the induction of PDAC cell anchorage-independent growth. |
| T13 |
1842-1959 |
Sentence |
denotes |
Our data indicate that hyper-O-GlcNAcylation is anti-apoptotic and contributes to NF-κB oncogenic activation in PDAC. |
