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Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma

Oncogene‐derived metabolic reprogramming is important for anabolic growth of cancer cells, which is now considered to be not simply rely on glycolysis. Pentose phosphate pathway and tricarboxylic acid cycle also play pivotal roles in helping cancer cells to meet their anabolic and energy demands. Th...

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Autores principales: Yang, Chun, Cui, Xiao‐wen, Ding, Zhi‐wen, Jiang, Tian‐yi, Feng, Xiao‐fan, Pan, Yu‐fei, Lin, Yun‐kai, Shang, Tai‐yu, Wang, Qing, Pan, Jian, Wang, Jian, Wang, Hong‐yang, Dong, Li‐wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746032/
https://www.ncbi.nlm.nih.gov/pubmed/36114745
http://dx.doi.org/10.1111/cas.15593
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author Yang, Chun
Cui, Xiao‐wen
Ding, Zhi‐wen
Jiang, Tian‐yi
Feng, Xiao‐fan
Pan, Yu‐fei
Lin, Yun‐kai
Shang, Tai‐yu
Wang, Qing
Pan, Jian
Wang, Jian
Wang, Hong‐yang
Dong, Li‐wei
author_facet Yang, Chun
Cui, Xiao‐wen
Ding, Zhi‐wen
Jiang, Tian‐yi
Feng, Xiao‐fan
Pan, Yu‐fei
Lin, Yun‐kai
Shang, Tai‐yu
Wang, Qing
Pan, Jian
Wang, Jian
Wang, Hong‐yang
Dong, Li‐wei
author_sort Yang, Chun
collection PubMed
description Oncogene‐derived metabolic reprogramming is important for anabolic growth of cancer cells, which is now considered to be not simply rely on glycolysis. Pentose phosphate pathway and tricarboxylic acid cycle also play pivotal roles in helping cancer cells to meet their anabolic and energy demands. The present work focused on gankyrin, a relatively specific oncogene in hepatocellular carcinoma (HCC), and its impact on glycolysis and mitochondrial homeostasis. Metabolomics, RNA‐seq analysis, and subsequent conjoint analysis illustrated that gankyrin regulated the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and mitochondrial function and homeostasis, which play pivotal roles in tumor development. Mechanistically, gankyrin was found to modulate HCC metabolic reprogramming via TIGAR. Gankyrin positively regulated the transcription of TIGAR through Nrf2, which bound to the antioxidant response elements (AREs) in the promoter of TIGAR. Interestingly, TIGAR feedback regulated the transcription of Nrf2 and subsequently gankyrin by promoting nuclear importation of PGC1α. The loop between gankyrin, Nrf2, and TIGAR accelerated glucose metabolism toward the PPP and TCA cycle, which provided vital building blocks, such as NADPH, ATP, and ribose of tumor and further facilitated the progression of HCC.
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spelling pubmed-97460322022-12-14 Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma Yang, Chun Cui, Xiao‐wen Ding, Zhi‐wen Jiang, Tian‐yi Feng, Xiao‐fan Pan, Yu‐fei Lin, Yun‐kai Shang, Tai‐yu Wang, Qing Pan, Jian Wang, Jian Wang, Hong‐yang Dong, Li‐wei Cancer Sci Original Articles Oncogene‐derived metabolic reprogramming is important for anabolic growth of cancer cells, which is now considered to be not simply rely on glycolysis. Pentose phosphate pathway and tricarboxylic acid cycle also play pivotal roles in helping cancer cells to meet their anabolic and energy demands. The present work focused on gankyrin, a relatively specific oncogene in hepatocellular carcinoma (HCC), and its impact on glycolysis and mitochondrial homeostasis. Metabolomics, RNA‐seq analysis, and subsequent conjoint analysis illustrated that gankyrin regulated the pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and mitochondrial function and homeostasis, which play pivotal roles in tumor development. Mechanistically, gankyrin was found to modulate HCC metabolic reprogramming via TIGAR. Gankyrin positively regulated the transcription of TIGAR through Nrf2, which bound to the antioxidant response elements (AREs) in the promoter of TIGAR. Interestingly, TIGAR feedback regulated the transcription of Nrf2 and subsequently gankyrin by promoting nuclear importation of PGC1α. The loop between gankyrin, Nrf2, and TIGAR accelerated glucose metabolism toward the PPP and TCA cycle, which provided vital building blocks, such as NADPH, ATP, and ribose of tumor and further facilitated the progression of HCC. John Wiley and Sons Inc. 2022-10-07 2022-12 /pmc/articles/PMC9746032/ /pubmed/36114745 http://dx.doi.org/10.1111/cas.15593 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Yang, Chun
Cui, Xiao‐wen
Ding, Zhi‐wen
Jiang, Tian‐yi
Feng, Xiao‐fan
Pan, Yu‐fei
Lin, Yun‐kai
Shang, Tai‐yu
Wang, Qing
Pan, Jian
Wang, Jian
Wang, Hong‐yang
Dong, Li‐wei
Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title_full Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title_fullStr Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title_full_unstemmed Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title_short Gankyrin and TIGAR cooperatively accelerate glucose metabolism toward the PPP and TCA cycle in hepatocellular carcinoma
title_sort gankyrin and tigar cooperatively accelerate glucose metabolism toward the ppp and tca cycle in hepatocellular carcinoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9746032/
https://www.ncbi.nlm.nih.gov/pubmed/36114745
http://dx.doi.org/10.1111/cas.15593
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