摘要
ATP柠檬酸裂解酶(ACLY))是与葡萄糖代谢相关的脂质形成过程中一个重要的酶,可催化转化柠檬酸变成草酰乙酸(OAA)和乙酰辅酶A。膜形成时脂质的合成需要获得期间的乙酰辅酶a、以及组蛋白乙酰化反应调节某些蛋白的表达异常增生的癌细胞。研究显示ACLY在肿瘤发生的作用是通过激活Akt蛋白激酶信号增加了酶的水平从而增加代谢活动。进一步的证据表明参与脂质生物合成的酶在癌症细胞增殖和进展过程中发挥重要作用。在许多癌症类型如胶质母细胞瘤、结直肠癌、乳腺癌、非小细胞肺癌、肝癌等;发现与正常细胞相比ACLY的水平相当高。癌症细胞生长相关的ACLY超表达可以用化学抑制剂或抑制ace基因进行抑制。抑制 ACLY导致癌症细胞代谢的变化,促进肿瘤的生长和扩散。本文总结了 ACLY在癌症发展和其抑制剂治疗癌症的作用。
关键词: 乙酰辅酶a
Current Drug Targets
Title:ATP Citrate Lyase (ACLY): A Promising Target for Cancer Prevention and Treatment
Volume: 16 Issue: 2
Author(s): Amrita Devi Khwairakpam, Mayengbam Singh Shyamananda, Bethsebie Lalduhsaki Sailo, Sivakumar Raju Rathnakaram, Ganesan Padmavathi, Jibon Kotoky and Ajaikumar B. Kunnumakkara
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关键词: 乙酰辅酶a
摘要: ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. The obtained acetyl-CoA is required for lipid synthesis during membrane biogenesis, as well as for histone acetylation reactions to regulate the expression of certain proteins in aberrantly proliferating cancer cells. Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene. Inhibition of ACLY leads to changes in cancer cell metabolism that promotes tumor growth and proliferation. This review summarizes the role of ACLY in cancer development and its inhibitors in cancer treatment.
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Amrita Devi Khwairakpam , Mayengbam Singh Shyamananda , Bethsebie Lalduhsaki Sailo , Sivakumar Raju Rathnakaram , Ganesan Padmavathi , Jibon Kotoky and Ajaikumar B. Kunnumakkara , ATP Citrate Lyase (ACLY): A Promising Target for Cancer Prevention and Treatment, Current Drug Targets 2015; 16 (2) . https://dx.doi.org/10.2174/1389450115666141224125117
DOI https://dx.doi.org/10.2174/1389450115666141224125117 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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