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Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-11 , DOI: 10.1038/s41419-019-2072-5 Yongsheng Jiang 1, 2 , Ruizhe He 1 , Yuhong Jiang 3 , Dejun Liu 1 , Lingye Tao 1 , Minwei Yang 1 , Chaoyi Lin 1 , Yang Shen 1 , Xueliang Fu 1 , Jianyu Yang 1 , Jiao Li 4 , Yanmiao Huo 1 , Rong Hua 1 , Wei Liu 1 , Junfeng Zhang 1 , Baiyong Shen 2 , Zhigang Zhang 5 , Yongwei Sun 1
Cell Death & Disease ( IF 8.1 ) Pub Date : 2019-12-11 , DOI: 10.1038/s41419-019-2072-5 Yongsheng Jiang 1, 2 , Ruizhe He 1 , Yuhong Jiang 3 , Dejun Liu 1 , Lingye Tao 1 , Minwei Yang 1 , Chaoyi Lin 1 , Yang Shen 1 , Xueliang Fu 1 , Jianyu Yang 1 , Jiao Li 4 , Yanmiao Huo 1 , Rong Hua 1 , Wei Liu 1 , Junfeng Zhang 1 , Baiyong Shen 2 , Zhigang Zhang 5 , Yongwei Sun 1
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Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion.
中文翻译：
转录因子NFAT5通过PGK1的转录促进糖酵解表型的重新连接和胰腺癌的进展。
缺氧和血管瘤微环境是胰腺导管腺癌（PDAC）的主要标志，其中糖酵解对肿瘤的生存和增殖至关重要。关于活化的T细胞5（NFAT5）的核因子在癌症中的作用的研究很少。在这里，我们探讨了NFAT5对PDAC生物学行为的影响及其潜在机制。我们证明了NFAT5在PDAC中高表达，并且与不良预后有关。敲除NFAT5会导致由异常的Warburg效应引起的肿瘤细胞增殖受损。在机械上，磷酸甘油酸激酶1（PGK-1）是NFAT5的靶基因，它是糖酵解中第一个产生ATP的酶，已被证实。PGK1的过表达损害了体外和体内NFAT5敲低引起的异常肿瘤行为。临床样本接受正电子发射断层扫描计算机断层扫描（PET-CT）检查，并收集KrasG12D / + / Trp53R172H / + / Pdx1-Cre（KPC）小鼠以支持我们的结论。
更新日期：2019-12-11
中文翻译：
转录因子NFAT5通过PGK1的转录促进糖酵解表型的重新连接和胰腺癌的进展。
缺氧和血管瘤微环境是胰腺导管腺癌（PDAC）的主要标志，其中糖酵解对肿瘤的生存和增殖至关重要。关于活化的T细胞5（NFAT5）的核因子在癌症中的作用的研究很少。在这里，我们探讨了NFAT5对PDAC生物学行为的影响及其潜在机制。我们证明了NFAT5在PDAC中高表达，并且与不良预后有关。敲除NFAT5会导致由异常的Warburg效应引起的肿瘤细胞增殖受损。在机械上，磷酸甘油酸激酶1（PGK-1）是NFAT5的靶基因，它是糖酵解中第一个产生ATP的酶，已被证实。PGK1的过表达损害了体外和体内NFAT5敲低引起的异常肿瘤行为。临床样本接受正电子发射断层扫描计算机断层扫描（PET-CT）检查，并收集KrasG12D / + / Trp53R172H / + / Pdx1-Cre（KPC）小鼠以支持我们的结论。
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