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    Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis. Hu Hongli,Zhu Wenwei,Qin Jun,Chen Min,Gong Liyan,Li Long,Liu Xiangyuan,Tao Yongzhen,Yin Huiyong,Zhou Hu,Zhou Lisha,Ye Dan,Ye Qinghai,Gao Daming Hepatology (Baltimore, Md.) Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein-binding protein-associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. CONCLUSION:These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515-528). 10.1002/hep.28887
    Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Broutier Laura,Mastrogiovanni Gianmarco,Verstegen Monique Ma,Francies Hayley E,Gavarró Lena Morrill,Bradshaw Charles R,Allen George E,Arnes-Benito Robert,Sidorova Olga,Gaspersz Marcia P,Georgakopoulos Nikitas,Koo Bon-Kyoung,Dietmann Sabine,Davies Susan E,Praseedom Raaj K,Lieshout Ruby,IJzermans Jan N M,Wigmore Stephen J,Saeb-Parsy Kourosh,Garnett Mathew J,van der Laan Luc Jw,Huch Meritxell Nature medicine Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease. 10.1038/nm.4438