FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3133684188> ?p ?o ?g. }

• W3133684188 abstract "Although cancer cells are frequently faced with a nutrient- and oxygen-poor microenvironment, elevated hexosamine-biosynthesis pathway (HBP) activity and protein O-GlcNAcylation (a nutrient sensor) contribute to rapid growth of tumor and are emerging hallmarks of cancer. Inhibiting O-GlcNAcylation could be a promising anticancer strategy. The gluconeogenic enzyme phosphoenolpyruvate carboxykinase 1 (PCK1) is downregulated in hepatocellular carcinoma (HCC). However, little is known about the potential role of PCK1 in enhanced HBP activity and HCC carcinogenesis under glucose-limited conditions. In this study, PCK1 knockout markedly enhanced the global O-GlcNAcylation levels under low-glucose conditions. Mechanistically, metabolic reprogramming in PCK1-loss hepatoma cells led to oxaloacetate accumulation and increased de novo uridine triphosphate synthesis contributing to uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) biosynthesis. Meanwhile, deletion of PCK1 also resulted in AMPK-GFAT1 axis inactivation, promoting UDP-GlcNAc synthesis for elevated O-GlcNAcylation. Notably, lower expression of PCK1 promoted CHK2 threonine 378 O-GlcNAcylation, counteracting its stability and dimer formation, increasing CHK2-dependent Rb phosphorylation and HCC cell proliferation. Moreover, aminooxyacetic acid hemihydrochloride and 6-diazo-5-oxo-L-norleucine blocked HBP-mediated O-GlcNAcylation and suppressed tumor progression in liver-specific Pck1-knockout mice. We reveal a link between PCK1 depletion and hyper-O-GlcNAcylation that underlies HCC oncogenesis and suggest therapeutic targets for HCC that act by inhibiting O-GlcNAcylation." @default.
• W3133684188 created "2021-03-15" @default.
• W3133684188 creator A5009553453 @default.
• W3133684188 creator A5012868175 @default.
• W3133684188 creator A5017280117 @default.
• W3133684188 creator A5020400859 @default.
• W3133684188 creator A5021486533 @default.
• W3133684188 creator A5022265396 @default.
• W3133684188 creator A5024164106 @default.
• W3133684188 creator A5029583137 @default.
• W3133684188 creator A5034314538 @default.
• W3133684188 creator A5040989553 @default.
• W3133684188 creator A5043226120 @default.
• W3133684188 creator A5043972313 @default.
• W3133684188 creator A5050868431 @default.
• W3133684188 creator A5054543838 @default.
• W3133684188 creator A5073531557 @default.
• W3133684188 creator A5081675173 @default.
• W3133684188 creator A5083374325 @default.
• W3133684188 creator A5084582460 @default.
• W3133684188 creator A5088868474 @default.
• W3133684188 date "2021-04-15" @default.
• W3133684188 modified "2023-10-18" @default.
• W3133684188 title "Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation" @default.
• W3133684188 cites W1553367038 @default.
• W3133684188 cites W1602446144 @default.
• W3133684188 cites W1879352431 @default.
• W3133684188 cites W1970255771 @default.
• W3133684188 cites W1982159046 @default.
• W3133684188 cites W1989157491 @default.
• W3133684188 cites W1996786134 @default.
• W3133684188 cites W2005959013 @default.
• W3133684188 cites W2007513097 @default.
• W3133684188 cites W2011628468 @default.
• W3133684188 cites W2019642182 @default.
• W3133684188 cites W2027899709 @default.
• W3133684188 cites W2028124816 @default.
• W3133684188 cites W2052543023 @default.
• W3133684188 cites W2057489420 @default.
• W3133684188 cites W2060799932 @default.
• W3133684188 cites W2069454964 @default.
• W3133684188 cites W2070923004 @default.
• W3133684188 cites W2071333117 @default.
• W3133684188 cites W2073296546 @default.
• W3133684188 cites W2077097398 @default.
• W3133684188 cites W2093090845 @default.
• W3133684188 cites W2094088765 @default.
• W3133684188 cites W2095987251 @default.
• W3133684188 cites W2104696999 @default.
• W3133684188 cites W2107498856 @default.
• W3133684188 cites W2110160400 @default.
• W3133684188 cites W2112516812 @default.
• W3133684188 cites W2124697228 @default.
• W3133684188 cites W2141227083 @default.
• W3133684188 cites W2167671063 @default.
• W3133684188 cites W2239497916 @default.
• W3133684188 cites W2464384284 @default.
• W3133684188 cites W2483556952 @default.
• W3133684188 cites W2503851771 @default.
• W3133684188 cites W2515188071 @default.
• W3133684188 cites W2518853513 @default.
• W3133684188 cites W2561797410 @default.
• W3133684188 cites W2587642665 @default.
• W3133684188 cites W2594070229 @default.
• W3133684188 cites W2600664554 @default.
• W3133684188 cites W2613539552 @default.
• W3133684188 cites W2621219284 @default.
• W3133684188 cites W2766200583 @default.
• W3133684188 cites W2783932169 @default.
• W3133684188 cites W2792807715 @default.
• W3133684188 cites W2795743867 @default.
• W3133684188 cites W2809778923 @default.
• W3133684188 cites W2810902531 @default.
• W3133684188 cites W2895610217 @default.
• W3133684188 cites W2898088739 @default.
• W3133684188 cites W2905965925 @default.
• W3133684188 cites W2921283762 @default.
• W3133684188 cites W2947415066 @default.
• W3133684188 cites W2951211477 @default.
• W3133684188 cites W2954280220 @default.
• W3133684188 cites W2957373505 @default.
• W3133684188 cites W2968014226 @default.
• W3133684188 cites W2980538229 @default.
• W3133684188 cites W2982442619 @default.
• W3133684188 cites W3004774663 @default.
• W3133684188 cites W3016145305 @default.
• W3133684188 cites W78381853 @default.
• W3133684188 cites W90010828 @default.
• W3133684188 doi "https://doi.org/10.1172/jci144703" @default.
• W3133684188 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8262473" @default.
• W3133684188 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33690219" @default.
• W3133684188 hasPublicationYear "2021" @default.
• W3133684188 type Work @default.
• W3133684188 sameAs 3133684188 @default.
• W3133684188 citedByCount "37" @default.
• W3133684188 countsByYear W31336841882021 @default.
• W3133684188 countsByYear W31336841882022 @default.
• W3133684188 countsByYear W31336841882023 @default.
• W3133684188 crossrefType "journal-article" @default.
• W3133684188 hasAuthorship W3133684188A5009553453 @default.

• next