دورية أكاديمية
LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer
| العنوان: | LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer |
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| المؤلفون: | Xu, Pan, Oosterveer, Maaike H., Stein, Sokrates, Demagny, Hadrien, Ryu, Dongryeol, Moullan, Norman, Wang, Xu, Can, Emine, Zamboni, Nicola, Comment, Arnaud, Auwerx, Johan, Schoonjans, Kristina |
| المصدر: | Xu , P , Oosterveer , M H , Stein , S , Demagny , H , Ryu , D , Moullan , N , Wang , X , Can , E , Zamboni , N , Comment , A , Auwerx , J & Schoonjans , K 2016 , ' LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer ' , Genes & Development , vol. 30 , no. 11 , pp. 1255-1260 . https://doi.org/10.1101/gad.277483.116Test |
| سنة النشر: | 2016 |
| المجموعة: | University of Groningen research database |
| مصطلحات موضوعية: | Hepatocellular carcinoma, cancer metabolism, nuclear receptor NR5A2, mitochondria, anaplerosis, mTOR, NADPH, RECEPTOR HOMOLOG-1, CELL-GROWTH, IN-VIVO, METABOLISM, PROLIFERATION, LRH-1, LIPOGENESIS, DEFICIENCY, PATHWAY, BIOLOGY |
| الوصف: | Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncanonical glutamine pathway that is reliant on the mitochondrial and cytosolic transaminases glutamate pyruvate transaminase 2 (GPT2) and glutamate oxaloacetate transaminase 1 (GOT1), which fuel anabolic metabolism. In particular, we show that gain and loss of function of hepatic LRH-1 modulate the expression and activity of mitochondrial glutaminase 2 (GLS2), the first and rate-limiting step of this pathway. Acute and chronic deletion of hepatic LRH-1 blunts the deamination of glutamine and reduces glutamine-dependent anaplerosis. The robust reduction in glutaminolysis and the limiting availability of a-ketoglutarate in turn inhibit mTORC1 signaling to eventually block cell growth and proliferation. Collectively, these studies highlight the importance of LRH-1 in coordinating glutamine-induced metabolism and signaling to promote hepatocellular carcinogenesis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://research.rug.nl/en/publications/c34317e6-6095-4bc9-a14a-26377213ca41Test |
| DOI: | 10.1101/gad.277483.116 |
| الإتاحة: | https://doi.org/10.1101/gad.277483.116Test https://hdl.handle.net/11370/c34317e6-6095-4bc9-a14a-26377213ca41Test https://research.rug.nl/en/publications/c34317e6-6095-4bc9-a14a-26377213ca41Test https://pure.rug.nl/ws/files/40762913/LRH_1_dependent_programming_of_mitochondrial_glutamine_processing_drives_liver_cancer.pdfTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.2FFD0461 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1101/gad.277483.116 |
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