Data from GOT2 Silencing Promotes Reprogramming of Glutamine Metabolism and Sensitizes Hepatocellular Carcinoma to Glutaminase Inhibitors

• DOI: 10.1158/0008-5472.c.6514128.v1
• Publication Date: 2023-03-31T21:15:58Z
• Authors: Yunzheng Li; Binghua Li; Yanchao Xu; Liyuan Qian; Tiancheng Xu; Gang Meng; Huan Li; Ye Wang; Laizhu Zhang; Xiang Jiang; Qi Liu; Yuanyuan Xie; Chunxiao Cheng; Beicheng Sun; Decai Yu
• Keywords: Glutaminase; Glutaminolysis; Reprogramming

<div>Abstract<p>Hepatocellular carcinoma (HCC) is one of the primary liver malignancies with a poor prognosis. Glutamic-oxaloacetic transaminase 2 (<i>GOT2</i>) highly tissue-specific gene in liver, but roles <i>GOT2</i> plays progression HCC remain unclear. Here, we report that downregulated tumor tissues and low expression associated advanced In cells, knockdown promoted proliferation, migration, invasion. mouse models HCC, loss growth as well hematogenous intrahepatic metastasis. Mechanistically, silencing GOT2 enhanced glutaminolysis, nucleotide synthesis, glutathione synthesis by reprogramming glutamine metabolism to support cellular antioxidant system, which activated PI3K/AKT/mTOR pathway contribute progression. Furthermore, was dependent on sensitive glutaminase inhibitor CB-839 <i>in vitro</i> vivo</i>. Overall, involved metabolic promote may serve therapeutic diagnostic target for HCC.</p>Significance:<p>Altered induced supports metastasis confers targetable vulnerability inhibitors.</p></div>