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Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress.
Oncogenesis ( IF 6.2 ) Pub Date : 2020-05-12 , DOI: 10.1038/s41389-020-0230-3
Jianhao Zhang 1 , Hongjian Duan 1 , Zhipeng Feng 1 , Xinwei Han 1 , Chaohui Gu 2
Affiliation  

Cancer cells adapt to nutrient-deprived tumor microenvironment during progression via regulating the level and function of metabolic enzymes. Acetyl-coenzyme A (AcCoA) is a key metabolic intermediate that is crucial for cancer cell metabolism, especially under metabolic stress. It is of special significance to decipher the role acetyl-CoA synthetase short chain family (ACSS) in cancer cells confronting metabolic stress. Here we analyzed the generation of lipogenic AcCoA in bladder cancer cells under metabolic stress and found that in bladder urothelial carcinoma (BLCA) cells, the proportion of lipogenic AcCoA generated from glucose were largely reduced under metabolic stress. Our results revealed that ACSS3 was responsible for lipogenic AcCoA synthesis in BLCA cells under metabolic stress. Interestingly, we found that ACSS3 was required for acetate utilization and histone acetylation. Moreover, our data illustrated that ACSS3 promoted BLCA cell growth. In addition, through analyzing clinical samples, we found that both mRNA and protein levels of ACSS3 were dramatically upregulated in BLCA samples in comparison with adjacent controls and BLCA patients with lower ACSS3 expression were entitled with longer overall survival. Our data revealed an oncogenic role of ACSS3 via regulating AcCoA generation in BLCA and provided a promising target in metabolic pathway for BLCA treatment.

中文翻译:

乙酰辅酶 A 合成酶 3 在代谢应激下促进膀胱癌细胞生长。

癌细胞在进展过程中通过调节代谢酶的水平和功能来适应营养匮乏的肿瘤微环境。乙酰辅酶 A (AcCoA) 是一种关键的代谢中间体,对癌细胞代谢至关重要,尤其是在代谢应激下。破译乙酰辅酶A合成酶短链家族(ACSS)在癌细胞面临代谢应激时的作用具有特殊意义。在这里,我们分析了代谢应激下膀胱癌细胞中脂肪生成AcCoA的生成,发现在膀胱尿路上皮癌(BLCA)细胞中,由葡萄糖生成的脂肪生成AcCoA的比例在代谢应激下大大减少。我们的结果表明,ACSS3 负责代谢应激下 BLCA 细胞中脂肪生成 AcCoA 的合成。有趣的是,我们发现 ACSS3 是乙酸盐利用和组蛋白乙酰化所必需的。此外,我们的数据表明 ACSS3 促进 BLCA 细胞生长。此外,通过分析临床样本,我们发现与相邻对照相比,BLCA样本中ACSS3的mRNA和蛋白水平均显着上调,并且ACSS3表达较低的BLCA患者具有更长的总生存期。我们的数据揭示了 ACSS3 通过调节 BLCA 中 AcCoA 生成的致癌作用,并为 BLCA 治疗的代谢途径提供了一个有前景的靶点。
更新日期:2020-05-12
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