Effects of ATP citrate lyase on lipid metabolism and tumor biological behavior of colon cancer cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

QIU Zhendong ^1,2 , DENG Wenhong ¹ , HONG Yupu ^1,2 , LI Man ^1,2 , YU Jia ¹ ,  WANG Weixing ¹

1. Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan 430060, P. R. China;

Corresponding author：

WANG Weixing, Email: sate.llite@163.com

Keywords：

colon cancer; ATP citrate lyase; lipid metabolism; proliferation; migration

DOI：

10.7507/1007-9424.202004133

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To study the effects of ATP citrate lyase (ACLY) gene on proliferation, apoptosis, invasion, and lipid metabolism of colon cancer cells.Methods Colon cancer cells HCT116 were transfected with lentiviral knockdown ACLY gene in vitro and divided into three groups according to cell treatment: HCT116 cells with ACLY gene knockdown as knockdown group, empty vector transfected cells as negative control group, and untreated colon cancer HCT116 cells as blank control group. After the stable new cell line was screened with puromycin, the expression of ACLY protein was detected by Western blot method, the lipid production of cells was detected by triglyceride test kit, the proliferation ability of cells was detected by CCK-8 method, the apoptosis rate was detected by flow cytometry, and the migration ability of cells was detected by cell scratch test.Results The cell survival rate of the knockdown group was lower than those of the blank control group and the negative control group at 120 h, but there was no significant difference among the three groups at 24 h and 48 h. Compared with the negative control group and the blank control group, the apoptosis rate in the knockdown group increased, the 24 h migration ability and the level of intracellular triglyceride decreased.Conclusion ACLY gene knockdown can inhibit the proliferation, apoptosis, and migration of colon cancer cells, and its mechanism may be related to the decrease of lipid synthesis ability of colon cancer cells.

Citation： QIU Zhendong, DENG Wenhong, HONG Yupu, LI Man, YU Jia, WANG Weixing. Effects of ATP citrate lyase on lipid metabolism and tumor biological behavior of colon cancer cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(1): 48-52. doi: 10.7507/1007-9424.202004133 Copy

1.	Tian L, Zhao ZF, Xie L, et al. Taurine up-regulated 1 accelerates tumorigenesis of colon cancer by regulating miR-26a-5p/MMP14/p38 MAPK/Hsp27 axis in vitro and in vivo. Life Sci, 2019, 239: 117035.
2.	Song Q, Zheng C, Jia J, et al. A probiotic spore-based oral autonomous nanoparticles generator for cancer therapy. Adv Mater, 2019, 31(43): e1903793.
3.	Zhu J, Thompson CB. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol, 2019, 20(7): 436-450.
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5.	Verschueren KHG, Blanchet C, Felix J, et al. Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Nature, 2019, 568(7753): 571-575.
6.	Wei J, Leit S, Kuai J, et al. An allosteric mechanism for potent inhibition of human ATP-citrate lyase. Nature, 2019, 568(7753): 566-570.
7.	Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res, 2012, 72(15): 3709-3714.
8.	Zhou J, Qu G, Zhang G, et al. Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway. J Exp Clin Cancer Res, 2019, 38(1): 96.
9.	Ference BA, Ray KK, Catapano AL, et al. Mendelian randomization study of ACLY and cardiovascular disease. N Engl J Med, 2019, 380(11): 1033-1042.
10.	Kumari R, Deshmukh RS, Das S. Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis. Nat Commun, 2019, 10(1): 4255.
11.	Wen J, Min X, Shen M, et al. ACLY facilitates colon cancer cell metastasis by CTNNB1. J Exp Clin Cancer Res, 2019, 38(1): 401.
12.	Wang J, Ye W, Yan X, et al. Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia. J Transl Med, 2019, 17(1): 149.
13.	Bauer DE, Hatzivassiliou G, Zhao F, et al. ATP citrate lyase is an important component of cell growth and transformation. Oncogene, 2005, 24(41): 6314-6322.
14.	Clarke A. Energy flow in growth and production. Trends Ecol Evol, 2019, 34(6): 502-509.
15.	Guo D, Bell EH, Mischel P, et al. Targeting SREBP-1-driven lipid metabolism to treat cancer. Curr Pharm Des, 2014, 20(15): 2619-2626.
16.	Lu J. The Warburg metabolism fuels tumor metastasis. Cancer Metastasis Rev, 2019, 38(1-2): 157-164.
17.	Comerford SA, Huang Z, Du X, et al. Acetate dependence of tumors. Cell, 2014, 159(7): 1591-1602.
18.	Xiang AS, Kingwell BA. Rethinking good cholesterol: a clinicians’ guide to understanding HDL. Lancet Diabetes Endocrinol, 2019, 7(7): 575-582.
19.	Dutta A, Sharma-Walia N. Curbing lipids: impacts on cancer and viral infection. Int J Mol Sci, 2019, 20(3): 644.
20.	Lee JV, Berry CT, Kim K, et al. Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca²⁺-NFAT signaling. Genes Dev, 2018, 32(7-8): 497-511.
21.	Karlstaedt A, Zhang X, Vitrac H, et al. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc Natl Acad Sci U S A, 2016, 113(37): 10436-10441.
22.	Lin R, Tao R, Gao X, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell, 2013, 51(4): 506-518.
23.	Lucenay KS, Doostan I, Karakas C, et al. Cyclin E associates with the lipogenic enzyme ATP-citrate lyase to enable malignant growth of breast cancer cells. Cancer Res, 2016, 76(8): 2406-2418.
24.	Zaidi N, Royaux I, Swinnen JV, et al. ATP citrate lyase knockdown induces growth arrest and apoptosis through different cell- and environment-dependent mechanisms. Mol Cancer Ther, 2012, 11(9): 1925-1935.

1. Tian L, Zhao ZF, Xie L, et al. Taurine up-regulated 1 accelerates tumorigenesis of colon cancer by regulating miR-26a-5p/MMP14/p38 MAPK/Hsp27 axis in vitro and in vivo. Life Sci, 2019, 239: 117035.
2. Song Q, Zheng C, Jia J, et al. A probiotic spore-based oral autonomous nanoparticles generator for cancer therapy. Adv Mater, 2019, 31(43): e1903793.
3. Zhu J, Thompson CB. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol, 2019, 20(7): 436-450.
4. Kedia-Mehta N, Finlay DK. Competition for nutrients and its role in controlling immune responses. Nat Commun, 2019, 10(1): 2123.
5. Verschueren KHG, Blanchet C, Felix J, et al. Structure of ATP citrate lyase and the origin of citrate synthase in the Krebs cycle. Nature, 2019, 568(7753): 571-575.
6. Wei J, Leit S, Kuai J, et al. An allosteric mechanism for potent inhibition of human ATP-citrate lyase. Nature, 2019, 568(7753): 566-570.
7. Zaidi N, Swinnen JV, Smans K. ATP-citrate lyase: a key player in cancer metabolism. Cancer Res, 2012, 72(15): 3709-3714.
8. Zhou J, Qu G, Zhang G, et al. Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway. J Exp Clin Cancer Res, 2019, 38(1): 96.
9. Ference BA, Ray KK, Catapano AL, et al. Mendelian randomization study of ACLY and cardiovascular disease. N Engl J Med, 2019, 380(11): 1033-1042.
10. Kumari R, Deshmukh RS, Das S. Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis. Nat Commun, 2019, 10(1): 4255.
11. Wen J, Min X, Shen M, et al. ACLY facilitates colon cancer cell metastasis by CTNNB1. J Exp Clin Cancer Res, 2019, 38(1): 401.
12. Wang J, Ye W, Yan X, et al. Low expression of ACLY associates with favorable prognosis in acute myeloid leukemia. J Transl Med, 2019, 17(1): 149.
13. Bauer DE, Hatzivassiliou G, Zhao F, et al. ATP citrate lyase is an important component of cell growth and transformation. Oncogene, 2005, 24(41): 6314-6322.
14. Clarke A. Energy flow in growth and production. Trends Ecol Evol, 2019, 34(6): 502-509.
15. Guo D, Bell EH, Mischel P, et al. Targeting SREBP-1-driven lipid metabolism to treat cancer. Curr Pharm Des, 2014, 20(15): 2619-2626.
16. Lu J. The Warburg metabolism fuels tumor metastasis. Cancer Metastasis Rev, 2019, 38(1-2): 157-164.
17. Comerford SA, Huang Z, Du X, et al. Acetate dependence of tumors. Cell, 2014, 159(7): 1591-1602.
18. Xiang AS, Kingwell BA. Rethinking good cholesterol: a clinicians’ guide to understanding HDL. Lancet Diabetes Endocrinol, 2019, 7(7): 575-582.
19. Dutta A, Sharma-Walia N. Curbing lipids: impacts on cancer and viral infection. Int J Mol Sci, 2019, 20(3): 644.
20. Lee JV, Berry CT, Kim K, et al. Acetyl-CoA promotes glioblastoma cell adhesion and migration through Ca²⁺-NFAT signaling. Genes Dev, 2018, 32(7-8): 497-511.
21. Karlstaedt A, Zhang X, Vitrac H, et al. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart. Proc Natl Acad Sci U S A, 2016, 113(37): 10436-10441.
22. Lin R, Tao R, Gao X, et al. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell, 2013, 51(4): 506-518.
23. Lucenay KS, Doostan I, Karakas C, et al. Cyclin E associates with the lipogenic enzyme ATP-citrate lyase to enable malignant growth of breast cancer cells. Cancer Res, 2016, 76(8): 2406-2418.
24. Zaidi N, Royaux I, Swinnen JV, et al. ATP citrate lyase knockdown induces growth arrest and apoptosis through different cell- and environment-dependent mechanisms. Mol Cancer Ther, 2012, 11(9): 1925-1935.

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Effects of ATP citrate lyase on lipid metabolism and tumor biological behavior of colon cancer cells

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