Khwairakpam Amrita Devi, Shyamananda Mayengbam Singh, Sailo Bethsebie Lalduhsaki, Rathnakaram Sivakumar Raju, Padmavathi Ganesan, Kotoky Jibon, Kunnumakkara Ajaikumar B
Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati, Assam-781039, India.
Curr Drug Targets. 2015;16(2):156-63. doi: 10.2174/1389450115666141224125117.
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.
ATP柠檬酸裂解酶（ACLY）是一种参与脂质生物合成且与葡萄糖代谢相关的重要酶，它催化柠檬酸转化为草酰乙酸（OAA）和乙酰辅酶A。生成的乙酰辅酶A在膜生物合成过程中的脂质合成以及组蛋白乙酰化反应中是必需的，用于调节异常增殖的癌细胞中某些蛋白质的表达。研究表明ACLY在肿瘤发生中起作用，即该酶水平升高会通过激活Akt信号通路导致代谢活性增加。越来越多的证据表明，参与脂质生物合成的酶在癌细胞增殖和进展中起重要作用。在许多癌症类型中，如胶质母细胞瘤、结直肠癌、乳腺癌、非小细胞肺癌、肝细胞癌等，与正常细胞相比，已发现ACLY水平相当高。使用化学抑制剂或敲低ACLY基因可抑制与ACLY过表达相关的癌细胞生长。抑制ACLY会导致促进肿瘤生长和增殖的癌细胞代谢变化。本综述总结了ACLY在癌症发展中的作用及其抑制剂在癌症治疗中的作用。
